To develop novel molecular diagnostic tools that will change how healthcare providers manage their patients.
Transcriptome Sciences Inc. (TSI), a privately held Alberta research company incorporated in 2008, is the commercial spin-off of the Alberta Transplant Applied Genomics Centre (ATAGC) at the University of Alberta in Edmonton, Canada. TSI is a University of Alberta research company dedicated to discovering the molecular basis of disease states and seeking commercial applications that improve treatments and outcomes. The result is an extensive and growing proprietary database consisting of clinical, histological, and gene expression findings from these biopsies supplemented with patient outcomes. TSI’s database forms the basis of the Molecular Microscope®Diagnostic (MMDx) System, a novel central diagnostic process for the assessment of organ disease states with unparalleled precision and accuracy. One Lambda (Thermo Fisher Scientific’s Brand) has an exclusive licensing agreement with TSI to access MMDx technology. To view the MMDx brochure, click here.
Transcriptome Sciences Inc. (TSI) is dedicated to commercializing its unique capabilities in the molecular basis of disease states to provide improved treatments and outcomes for patients.
Dr. Halloran is a clinician-scientist with extensive research experience in basic immunology, clinical research, and microarrays. He currently leads the Alberta Transplant Applied Genomics Center (ATAGC) and is a Professor of Medicine (Nephrology) at the University of Alberta in Edmonton. He has more than 400 peer-reviewed publications in transplantation and inflammatory diseases. He is an officer of the Order of Canada, a Fellow of the Royal Society of Canada, has held the Muttart Chair in Clinical Molecular Immunology and Autoimmunity from the Muttart Foundation since 1993, was the founding editor of the American Journal of Transplantation, the first recipient of the Paul Terasaki Prize, and an elected member of the American Society for Clinical Investigation. He holds an MD from the University of Toronto and a PhD from the University of London.
Team Leader & Senior Scientist
Dr. Famulski is an experienced research scientist and manager. In his role as Team Leader he oversees the daily operations of ATAGC and works closely with TSI. He holds a PhD and a DSc from the Nencki Institute of Experimental Biology at the Polish Academy of Sciences.
Business & Operations Manager
Dr. Polakowski is an experienced life sciences professional with broad skills spanning R&D, Product Development, Technology Transfer, and Business Development. He has worked in the Alberta life sciences sector for over 14 years, including local health technology startups. He possesses a solid understanding of health technology commercialization and innovation. At TSI he is responsible for daily company operations, business development, partner relations, finances, and HR. He holds a BSc in Chemistry from McMaster University and a PhD in Chemistry from the University of Alberta.
Data Analyst & Research Administration Manager
Jessica holds a BSc in Actuarial Science with Business Minor from the University of Alberta. Drawing upon her mathematical and programming background, she performs statistical and exploratory analyses on organ gene expression data from the TSI disease databases. She also provides collaborative support in manuscript development and editing, assists with the submission of manuscripts as well as being the webmaster of this website.
Senior Research Scientist
Dr. Madill-Thomsen is a Senior Research Scientist working with Phil Halloran’s team at the University of Alberta in Edmonton, Canada. Originally graduating with distinction from a basic science undergraduate program (B.Sc. Chemistry), she now holds a Ph.D. in Medicine from the University of Alberta with a focus on the application of microarrays in diagnostics in transplants and in native organs and has expertise in machine learning, statistics, clinical trials, and wet-lab techniques. Dr. Madill-Thomsen’s research focuses on the development and calibration of precision medicine diagnostic systems using genome-wide expression (The Molecular Microscope® System ‘MMDx’) to diagnose rejection and injury in liver, kidney, heart, and lung transplants. With a decade of research experience, her work now involves collaborations with key opinion leaders in more than 80 centers around the world. Most recently, she has been developing new diagnostic methods for detecting unique injury phenotypes and varying forms of rejection in a population of liver transplants, assessing the spectrum of abnormalities in kidney transplant biopsies without clinical or molecular rejection, and creating new classifiers for assessing donor-specific antibody in lung transplant biopsies.
Senior Laboratory Technologist
Senior Laboratory Scientist
Dr. Mackova is a research scientist with over 20 years of experience in biomedical research. She has worked on various research projects at the University of Alberta, including Microbiology, Immunology, Perinatal and Cardiovascular research. She has presented her work at numerous international conferences and published in peer reviewed journals. At TSI, she is responsible for RNA microarray analysis, QC and other laboratory assessments, as well as signing out MMDx reports and communicating the results to clinicians from collaborating medical centers around the world. She also provides training and technology transfer support to our clinical laboratory partners. She holds an MSc and a PhD in Human and Animal Physiology from Comenius University and Slovak Academy of Sciences. She completed a Postdoctoral fellowship at University of Alberta.
Senior Data Scientist
Dr. Gauthier received his PhD training as an experimental biologist in the field of ecotoxicology. He has developed predictive multivariate models to provide regulatory guidance for pollutant mixtures, helped bridge the gap between endocrinology and behavioural toxicology by developing drug biosensor models with zebrafish embryo neurobehavioural biomarkers, and has published critical review papers outlining the molecular and cellular mechanisms of mixture toxicology and risk assessment of pollutants in the Arctic. Dr. Gauthier’s work has involved diverse statistical and programming needs, and he has produced a variety of novel inferential methods. Dr. Gauthier’s true passion lies in exploring and developing new bioinformatic tools, and TSI is excited to have him on board to contribute to the precision and accuracy of molecular diagnoses of organ transplant rejection.
Holding a BSc in Biological Sciences and an MSc in Cells, Physiology, and Developmental Biology from the University of Alberta, Michelle assists in daily lab wet lab work, such as processing samples and conducting other laboratory assessments. She also works as a go-between between the lab and other aspects of TSI, performing duties such as data management and IT as needed.
Transcriptome Sciences Inc.’s (TSI) Board is composed of recognized business and academic leaders:
CEO, Ciclofilin Pharmaceuticals
Dr. Foster was the founding CEO of Isotechnika Pharma Inc. (Edmonton, 1993) and is the Founder and CEO of Ciclofilin Pharmaceuticals (San Diego). As a respected executive, he has served in multiple capacities in academia and the biotechnology industry in Canada and abroad. He is named as an inventor on 242 patents. He led the discovery of the immunosuppressive drug Voclosporin and the diagnostic test kit, Helikit, for the diagnosis of H.pylori. He holds an MPharm and PhD from the University of Alberta.
Dr. Halloran is a clinician scientist with extensive research experience in basic immunology, clinical research, and microarrays. He currently leads the Alberta Transplant Applied Genomics Center (ATAGC) at the University of Alberta in Edmonton. He has more than 400 peer reviewed publications in transplantation and inflammatory diseases. He is an officer of the Order of Canada, a Fellow of the Royal Society of Canada, the first recipient of the Paul Terasaki Prize, and an elected member of the American Society for Clinical Investigatiton. He holds an MD from the University of Toronto and a PhD from the University of London.
Associate, Kingsgate Legal
Ms. Halloran is a commercial litigator with a primary focus on contractual disputes, product liability and risk management. She has extensive experience in a number of industry sectors, including energy, professional services and insurance. She is a Member of the Law Society of Alberta, the Law Society of Upper Canada and the Canadian Bar Association. She holds an LLB from the University of Alberta, an MA from Brock University, and a BA (with Distinction) from the University of Alberta.
TSI's Professional Advisors
Legal Advisors: Kingsgate Legal 2100 Bell Tower 10104 – 103 Avenue Edmonton, Alberta T5J-0H8 Phone: 1-888-488-4006
Bankers: Royal Bank of Canada 10107 Jasper Avenue Edmonton, AB T5J 1W9 Phone : (780) 448-6611
Patent Attorneys: Fish & Richardson P.C. 3300 Dain Rauscher Plaza 60 South Sixth Street Minneapolis, MN 55402 Phone: (612) 337-2565
Insurance Broker: AON Reed Stenhouse Inc. #900, 10025 102A Avenue Edmonton, AB T5J 0Y2 Phone: (780) 423-9801
Accountant: Grant Thornton LLP 1701 Rice Howard Place 2 10060 Jasper Avenue NW Edmonton, AB T5J 3R8 Phone: (780) 422-7114
Transcriptome Sciences Inc. (TSI) is always interested in hearing from qualified candidates seeking work in the molecular diagnostics sector, and welcomes resumes and CVs sent to firstname.lastname@example.org Please check back regularly for new job postings and information on available positions.
The current standard for diagnosing and detecting organ disease from tissue biopsies is histology, the microscopic examination of processed tissue samples using various stains. This process is highly subjective and prone to relatively high error rates and disagreement among observers. Moreover, many types of changes in disease states are molecular but not microscopically detectable. These high error rates often result in inappropriate treatments for patients, leading to higher costs and poor outcomes. In the post-genomic era, molecular diagnostics are being developed to address the unmet need for precision in diagnostics. Gene expression data can now be used to objectively assess disease states, adding predictive value to conventional methods. Microarrays (gene chips) are the best established method for studying gene expression in biopsies. Coupled with sophisticated statistical and machine learning methods, microarrays can identify gene expression patterns relatively specific for different disease states. Changes in gene expression are early indicators of changes in a tissue, and can be measured objectively and quantitatively, unlike opinion-based microscopic assessment of biopsies. TSI is also exploring the potential advantages of RNA sequencing.
TSI, in partnership with the ATAGC, is engaged in research collaborations with many centers in Canada, the United States, Europe, Australia, and Asia. There are limitations in the conventional opinion-based histology and laboratory-developed tests such as DSA and C4d staining, thus future biopsy assessment will require centralized molecular tests with evidence-based interpretation. The MMDx system incorporates strengths of each platform, both histology and molecular assessment. Gene expression measurements, or “classifiers”, were used to develop scores for diagnosing T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), and all rejection. Each classifier generates a score indicating the probability of a conventional diagnosis, and these scores are then displayed on a report that is returned to the clinician. In addition, we developed a gene set that quantifies acute kidney injury (AKI). The TCMR classifier correlates with the histologic lesions of TCMR (infiltrate, tubulitis). The ABMR Score correlates with ABMR microcirculation lesions and with donor-specific antibodies (DSA). The ABMR Score has also been shown to strongly predict future graft loss. MMDx for kidney transplants requires one additional kidney tissue needle biopsy core beyond the usual two to three biopsy cores obtained for routine histopathology as standard of care. Currently, the MMDx for kidney is in use in a number of transplant centers in North America, Asia, Australia, and Europe. MMDx for kidney is available for reimbursement in the United States. To view the MMDx brochure, click here.
MMDx-Kidney Diagnostic System Extension
Calibrating circulating donor-derived cell-free DNA against molecular biopsy assessments.Investigators: Philip F Halloran, Jeff Reeve, Soroush Shojai, Sita Gourishankar, and the MMDx-Kidney Study Group (ClinicalTrials.gov NCT04239703) Biopsies both for indications and by protocol play an important role in managing organ transplants, but histology assessment has high interobserver disagreement (“noise”) and cannot assess recent tissue injury.To improve precision and accuracy of biopsy assessment, the Alberta Transplant Applied Genomics Centre of the University of Alberta ATAGC) has developed a new biopsy assessment system: the Molecular Microscope® Diagnostic System (MMDx), which measures global gene expression in the biopsy and uses ensembles of machine learning derived algorithms to diagnose rejection and injury. However, the decision to biopsy is often difficult for the clinician, and new tools for predicting abnormalities in the organ transplant are needed. A new blood-based test may guide decisions to biopsy: donor-derived cell-free DNA (DD-cfDNA). The donor kidney cells release DD-cfDNA during rejection and injury episodes. The Natera DD-cfDNA test is based on massively multiplexed PCR that targets 13,392 single nucleotide polymorphisms. Targeted sequences are then quantified by Next Generation Sequencing (mmPCR-NGS). The ATAGC cfDNA-MMDx study (“Trifecta”) will compare DD-cfDNA, DSA, and MMDx results in prospectively collected clinically indicated kidney transplant biopsies and accompanying blood samples from participating American and European centers. DD-cfDNA (Prospera® test; Natera Inc.) levels will be calibrated against the MMDx biopsy diagnoses of T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR, and its stages), and acute and chronic injury. The Trifecta study also includes donor-specific antibody (DSA) assessment by One Lambda. The DD-cfDNA will be calibrated for its ability to predict the MMDx phenotypes in the biopsy. The major trial objectives are 1.) to calibrate DD-cfDNA readings against the MMDx assessments of TCMR, ABMR, and injury; 2.) to optimize and quantify donor DNA measurements; 3.) to develop new treatment algorithms that incorporate both rejection mechanisms is kidney and release of donor DNA. We believe that calibrating the Prospera® DD-cfDNA test and One Lambda HLA typing results against MMDx will improve transplant patient care but also generate novel insights into clinical scenarios. In addition, DD-cfDNA testing plus MMDx may reduce unnecessary indication biopsies, and make the biopsies that are performed much more useful, and the management decisions more effective. More accurate diagnoses will lead to increasingly personalized treatment, superior endpoints for clinical trials of new agents, and prolonged graft survival.
TSI, in partnership with the ATAGC, is engaged in research collaborations with many centers in Canada, the United States, Europe, Australia, and Asia. The current standard method for diagnosis of organ rejection in heart transplants is microscopic assessment of a tissue biopsy, using the International Society for Heart and Lung Transplantation (ISHLT) classification system. However, recent studies have indicated that this system can produce incorrect diagnoses with potential harm to patients due to inappropriate treatment. MMDx system for heart transplants addresses the need for a more quantitative and objective approach to heart biopsy assessment by introducing molecular and diagnoses. Biopsies are interpreted based on their molecular and clinical characteristics, plus clinical and laboratory parameters, to give the diagnosis. MMDx will detect and/or assess T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), acute parenchymal injury (API), risk of failure, fibrosis, and cardiac allograft vasculopathy (CAV). The MMDx for heart is in use in a number of transplant centers in North America, Australia, and Europe. MMDx for heart is available for reimbursement in the United States. MMDx for heart transplants requires two additional endomyocardial biopsy (EMB) bites beyond the usual five to seven EMB bites obtained for routine histology as standard of care. To view the MMDx brochure, click here.
TSI, in partnership with the ATAGC, is engaged in research collaborations with many centers in Canada, the United States, Europe, Australia, and Asia. The current standard method for diagnosis of organ rejection in lung transplants is microscopic assessment of a transbronchial biopsy, using the International Society for Heart and Lung Transplantation (ISHLT) classification system. However, recent studies have indicated that this system can produce incorrect diagnoses with potential harm to patients due to inappropriate treatment. MMDx for lung transplants addresses the need for a more quantitative and objective approach to lung biopsy assessment by introducing a molecular diagnostic system. MMDx is studying transbronchial biopsies and is also exploring the potential of using mucosal biopsies which would be safer and more accessible. MMDx will detect and/or assess T cell-mediated rejection (TCMR), risk of failure, and chronic lung allograft dysfunction (CLAD). MMDx for lung began clinical trials in late 2016. MMDx system for lung transplants requires two additional lung tissue bites beyond the usual ten transbronchial biopsy bites obtained for routine histology as standard of care. To view the MMDx brochure, click here.
TSI, in partnership with the ATAGC, is engaged in research collaborations with many centers in Canada, the United States, Europe, Australia, and Asia. Liver transplantation is a remarkable success story in managing end stage liver disease, until recently heavily impacted by the influence of hepatitis C virus (HCV) which confused assessment of rejection. The emerging cures for HCV have created a new agenda for liver transplantation: improve understanding and diagnosis of T cell-mediated rejection (TCMR) and injury/fibrosis. Liver transplant management, however, presents a special case of a general problem: the unsatisfactory state of biopsy assessment by histology. MMDx system will assess the diagnostic and prognostic value of microarray analysis of biopsy specimens from liver allografts, and define the molecular phenotype of liver biopsy. It will also change care and outcomes in liver transplantation by developing microarray-based tests for liver biopsy specimens for the TCMR and acute and chronic liver injury. MMDx for liver began clinical trials in late 2018. MMDx for liver transplants requires half (3-5 mm) of the liver biopsy taken obtained for routine histology as standard of care. To view the MMDx brochure, click here.
More details on the upcoming MMDx® for Melanoma coming soon.
Inflammatory Bowel Disease
The current standard of care for diagnosing inflammatory bowel disease (IBD) and guiding IBD treatment is a combination of endoscopy, microscopic examination of intestinal tissue and measurement of markers in stool and blood. MMDx for assessing IBD has potential for improved precision and accuracy compared to conventional assessments. View the MMDx brochure here.
High costs and long timelines in drug development are largely due to inefficient target identification and development models. The Molecular Microscope® Diagnostic System (MMDx) can assist this process in several ways:
Better understanding of potential targets in terms of “gene and protein” function
Reliable gene expression information
Accurate quantifiable clinical trial endpoints
Transcriptome Sciences Inc. (TSI) is uniquely positioned to address all of these needs through its proprietary MMDx algorithms and database. Guiding the development of new and improved drugs is part of TSI’s mandate to foster an environment of enhanced patient care and better outcomes.
The current standard for diagnosing and detecting organ disease from tissue biopsies is by microscopic examination. This process, however, is different for each procedure and error-prone. Currently, molecular diagnostics are being developed to complement histological practices. Gene expression data can now be used to objectively assess disease states, and add predictive value to conventional methods. Transcriptome Sciences Inc. (TSI) is uniquely positioned to address all of these needs through its proprietary technology. With a complementary test capable of supplementing the current standard of care, better treatment plans can be developed. Through MMDx, TSI intends to provide health care practitioners with an improved understanding of diseases to augment diagnosis, treatment, and monitoring.
“…A powerful diagnostic strategy contributing to a better understanding of the specific causes of transplant injury. In ongoing intervention trials our group has learned that the Molecular Microscope® (MMDx) has the potential to substantially improve the accuracy of biopsy-based rejection diagnosis…” Dr. Georg Bohmig and Dr. Farsad Eskandary VIETAC, Medical University Vienna, Vienna, Austria
“The Molecular Microscope® (MMDx) has performed extremely well when compared with histology at our transplant center. Knowing this we have confidence in the MMDx when traditional diagnostic methods are ambiguous, such as in the case of ABMR.” Dr. Andrew Malone Washington University School of Medicine, St. Louis, MO, USA
“It is very exciting to see that Molecular Microscope® (MMDx) is moving to clinical practice.” Enver Akalin, MD Montefiore Medical Center, Bronx, NY, USA
“We have been using MMDx (Molecular Microscope®) … and have been very impressed with the results. In general, there is a high concordance with pathology results which gives the treating clinician more confidence in the diagnosis and management. In many cases, MMDx has provided greater insight and granular detail to our biopsy evaluation which has significantly helped in patient care. I believe that MMDx will remain a valuable tool for the care of our kidney transplant patients.” Dr. Gaurav Gupta VCU, Richmond, VA, USA
What is MMDx and how does it work?
A. The Molecular Microscope® (MMDx) is a molecular system for tissue biopsy analysis. RNA is extracted from the biopsy, then analyzed using microarray technology. Gene expression results are statistically compared to an established reference set of known biopsies to produce a report and diagnosis. This system complements histology, by offering a quantitative and objective method for tissue biopsy analysis. To view the MMDx brochure, click here.
A. A molecular classifier is a machine learning method that can predict something (e.g. diagnoses) based on the gene expression data output from the microarray analysis. This is done by the program ‘learning’ which expression patterns can recognize the differences between the samples, and combining these differences to generate a pattern that can be used to predict the diagnosis in future (unknown) samples.
How do I ship a sample?
A. Samples are shipped to Transcriptome Sciences Inc. in Edmonton, Canada using approved packaging materials provided by Transcriptome (TSI).
Biopsies are stabilized immediately after they are taken in a transport tube with RNAlater®
The sample transport tube is wrapped in absorbent tissue, and placed in a small biohazard bag
The biohazard bag is placed in a padded envelope
The padded envelope is packaged in a FedEx Pak with appropriate paperwork and waybill affixed
A. The Molecular Microscope® (MMDx) has compared very favorably to clinical opinion and local conventional assessment, with accuracy of 90% in TCMR and 78% in ABMR. In 275 feedback forms thus far, clinicians have indicated that 86% agreed with clinical judgment (with or without disagreement with histology), 84% indicated that MMDx invited more confidence for management decisions and that in 1/4 of biopsies the MMDx report would alter therapy and/or investigations.
Is MMDx safe for my patients?
A. MMDx requires only one biopsy beyond the standard of care, and poses minimal risk to your patient.
What information is required for submitting a sample?
A. The minimal information absolutely required for submitting a sample is the date of transplant and date of biopsy, though more information is useful and can make the diagnoses more relevant. Please email email@example.com for more details.
Is MMDx a central diagnostic system or a kit?
A. MMDx is a central diagnostic system.
For a current list of our publications, please click here. To view the MMDx brochure, click here.
News & Events
Hot off the press! New Trifecta Study manuscript in Transplantation!
Gene Expression Profiling for Molecular Biopsy Assessment
Post-transplant biopsy analyses are subjective and prone to debate.
Conventional assessments are currently the primary tool used for diagnosing injury and rejection but studies show that histology results are widely varied… The solution to this variance lies in game-changing automated molecular analysis to interpret the results.
Introducing the Molecular Microscope Diagnostic System™ (MMDx™): A diagnostic service that uses gene expression profiling to assess the presence of disease states in a transplant biopsy. Powered by machine learning and big data, MMDx generates information on the sample’s risk for T-cell and Antibody-mediated rejection, injury, and other conditions.
Here’s How MMDx works…
– During the standard biopsy procedure, take a portion of the sample and place it in the RNAlater solution included in your free collection kit. Then ship the kit to the reference lab at room temperature.
– Upon receipt, the sample is analyzed and matched against a reference set database with thousands of biopsies.
– Depending on the nature of the rejection or injury state, certain genes are activated in the transplanted tissue and will produce unique patterns of messenger RNA.
MMDx analyzes thousands of different messenger RNA to provide information about the health of the organ.
The results are posted on the MMDx portal in 1-2 business days and you’ll receive an email when the report is ready for review.
The technology is here and ready to be used to help patients receive better care.
MMDx is a Laboratory Developed Test that uses a GeneChip™ Custom Microarray to measure mRNA transcript levels in biopsies along with extensive big data derived from individuals and populations. The system combines these technologies to deliver objective and reproducible transplant biopsy assessments on a molecular level. MMDx complements conventional biopsy processing to improve the assessment of rejection and injury in transplanted organs.
Please join us for the 2021 ASHI Hybrid Annual Meeting where Dr. Halloran will be presenting “DSA-negative HLA antibody-negative molecular ABMR releases donor-derived cell-free DNA in the Trifecta study.“ Abstract details can be found here.
The Molecular Microscope® Diagnostic System (MMDx) will be featured in Natera Inc.’s Symposium on September 30th from 12:15 pm to 2:05 pm EDT. Registration details can be found here.
Integrating Molecular Approaches to Surveil Rejection: %dd-cfDNA, DSA, and Molecular (MMDx) Biopsy Assessment
Date/Time: Thursday, September 30, 2021 – 12:15 PM to 2:05 PM EDT
Hot off the press! New JASN manuscript
Hot off the press! Read our new manuscript in the Journal of the American Society of Nephrology: bit.ly/j2021040433
Donor-specific HLA antibody in kidney transplant patients with biopsies classified as no-rejection was more common than thought and associated with increased risk of kidney failure within 3 years
Dr. Philip Halloran to present at Indian Society of Heart and Lung Transplantation on January 23, 7:00 am to 7:20 am MST
Join Dr. Philip Halloran as he presents at the Indian Society for Heart and Lung Transplantation (INSHLT) on January 23, 7:00 am to 7:20 am MST. He will present “MMDx System for solid organ transplants especially heart and lung transplants“.
Hot off the press! Nature Scientific Reports paper!
Our most recent paper by Hruba et al has been published in Nature Scientific Reports titled, “Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts“. You can find it here: https://www.nature.com/articles/s41598-020-79332-9
Dr. Philip Halloran to present at the ILTS Webinar on December 7 at 7:00 am MT
Join the ILTS Webinar on “Markers of rejection and of tolerance in liver transplantation current tools and futures candidates” on December 7 at 7:00 am MT!
𝐏𝐡𝐢𝐥𝐢𝐩 𝐇𝐚𝐥𝐥𝐨𝐫𝐚𝐧, Josh Levitsky, Alberto Sanchez-Fueyo will discuss the different types of rejection, new tools for diagnosis, and best therapeutic options.
Fall 2020 Convocation Spotlight: Katelynn S. Madill-Thomsen, ’20 PhD in Medicine
Completing her doctoral studies in the time of COVID-19 brings the importance of science literacy and communication into sharper focus.
SALENA KITTERINGHAM – 17 November 2020
Katelynn S. Madill-Thomsen, ’20 PhD in Medicine
Katelynn S. Madill-Thomsen, ’20 PhD in Medicine, encourages her fellow Class of 2020 colleagues to take their unprecedented experiences of completing their programs in the midst of a pandemic as a prompt to continually become better communicators and ambassadors of science.
“Good science cannot stand alone; it also requires good communication to really make a difference,” she says. “It’s becoming more and more important to be able to communicate our findings and conclusions both to our peers and to the public and media, in a way that is simple and easily understood but not inaccurate.”
She says improving scientific literacy in the general public should be something every researcher strives for. “This gives the public more awareness of what’s happening in research, how it affects them, and how to critically evaluate fact from fiction in scenarios where science and medicine impact their daily lives.”
Read more about Madill-Thomsen’s most memorable lessons learned at the U of A.
Katelynn S. Madill-Thomsen, ’20 PhD in Medicine Specialization: Nephrology
Department of Medicine
Supervisor: Philip Halloran
Vibrant graduate student life at UAlberta
I was part of a group of students, led by Melissa Silva, who founded the Department of Medicine Graduate Students’ Association (DoM-GSA). We felt that providing the opportunity to collaborate, network and build community within the DoM would be beneficial for students.
I served with that group as president-elect from 2017 to 2018, then as president from 2018 to 2019. It was one of the highlights of my time at the U of A, and allowed me to get to know my peers much better than I might have otherwise.
We were able to gather for sessions on professional development, mental health, or games and movies, and I met so many talented, intelligent and kind students as a result. I really enjoyed my time working with the DoM-GSA and still value the relationships that came out of that experience.
The collective ‘zoom, zoom, zoom’ experience of the Class of 2020
Defending over Zoom was certainly memorable! It’s interesting being part of this particular group of students, who share the collective experience of having finished their program under these circumstances. It was a test of our determination and I’m so glad we were all able to persevere.
Can’t pick favourites
I enjoyed all of my classes and feel I benefited from each one of them (Introduction to Inflammation, Directed Studies in R Programming, Biostatistics and The Art of Grant Writing).
They were all challenging, given that my undergraduate background was in chemistry and this was all fairly unrelated to the classes I took for my graduate program. But my professors were all incredibly kind, patient and encouraging and I came out of each class being better informed and prepared for my career.
I do recall my time in The Art of Grant Writing especially fondly; this was an extremely challenging course but it’s made an enormous difference to me in terms of writing ability and was worth all the effort and time, since a research career depends on this skill.
High school mentor set the path to medicine
I’ve had many valuable mentors in my life. I had a chemistry teacher in high school who taught me via distance learning and had infectious passion for science. He would call me long-distance to explain the concepts and I ended up choosing to take Chemistry 30 early because he was such an effective educator. Sadly, he passed away from cancer the following year, and as a result I decided that I was eventually going to go into medical research.
I had a wonderful adviser in my undergraduate studies who was the first person to suggest that I consider a graduate degree and go even further into research. And I had a very encouraging and supportive supervisor (Philip Halloran) and committee (Brendan Halloran and Luis Hidalgo) during my PhD program who fully believed in my capabilities and pushed me through the enormous learning curve of this program.
I don’t think I can thank any of these people enough for having influenced me as much as they have.
Two greatest lessons gleaned from her time at U of A
Be patient with learning curves: There is an inflection point where suddenly a switch flips and things start to make sense. It goes from “I don’t get this” to “Wow, that does actually make sense, I can do this,” and that moment is worth all the struggle and effort and frustration because you earned it. I cannot describe the incredible feeling when you finally understand something or get an experiment to work or figure out a new research method after digging into it for a long time and wrestling with the details.
Critical thinking is absolutely essential: The more you learn in a graduate program, the more you become aware of all there is to know. You think that there are all these definitive concepts in science, but going in depth into the details shows you just how much there is left to discover and define. To do this as researchers, we have to be comfortable with and capable of critical thinking―examining the evidence, seeking wisdom and advice from research peers and having open minds and collaborative attitudes.
Drawing inspiration from the scientific community around her
Every time I hear a research talk about a new medical discovery and the impact it’s had on patient care and outcomes, I’m inspired to keep going.
There are so many areas of medicine where we can still make leaps and bounds forward in patient management and reducing mortality, and by doing our research work we can have a significant impact on someone else’s life! Much of my work has been in transplants, which in itself is a uniquely inspiring area of medicine where a death can result in life for another patient. I think about that every day.
I’d love to make a contribution to medicine and medical knowledge that would improve outcomes and reduce patient mortality in a tangible and demonstrable way. That would be very meaningful, and I plan on working very hard towards this.
Advice to those considering grad school
If you’re interested in graduate studies, do it! Graduate studies is such a departure from traditional educational experiences in that it’s so self-directed and open-ended. It forces you to critically think (a skill that’s more important in today’s world than perhaps ever before) and deal with setbacks and issues in real time. I found my time as a graduate student to be enormously beneficial; it showed me all the areas I excelled in as well as revealing areas I needed to work on and then gave me the time and resources to improve. I’ve definitely benefited from this degree, and can contribute more as a scientist because of it.
Check out our recently accepted manuscript at the American Journal of Transplantation!
Check out our recently accepted manuscript at AJT!
Genome-wide microarray analysis of kidney transplant biopsies discovers a novel increase in epithelial polarity genes that plays a major role in the fate of early kidney transplants but is suppressed in T cell-mediated rejection.
Dr. Philip Halloran has been named to the Mendez National Institute of Transplantation Foundation's Research Advisory Board
Dr. Philip Halloran has been named to the Mendez National Institute of Transplantation Foundation’s Research Advisory Board.
“I was long an admirer of the Mendez brothers and their contributions in transplantation, and was very impressed when they created MNITF. Too few agencies are operating to promote and fund transplant research. When I was asked to join the board, I was glad to be able to help this important agency.”
– Dr. Philip Halloran on what made him decide to join the MNITF RAB
Dr. Philip F. Halloran selected as the 2020 International Scholar Awardee by the American Society for Histocompatibility and Immunogenetics (ASHI)
Dr. Philip F. Halloran has been selected as the 2020 International Scholar Awardee by the American Society for Histocompatibility and Immunogenetics (ASHI). He will be presenting “The Trifecta Study: Calibrating circulating donor-derived cell-free DNA at the time of indication biopsies against the molecular phenotype of the biopsy” on Monday, October 19 at 11 am EST at the 2020 ASHI Virtual Annual Meeting. Trifecta (ClinicalTrials.gov # NCT04239703) is an international collaborative study by 31 investigators from 15 transplant centers in 6 countries to calibrate circulating cell-free donor DNA in transplant patients against the molecular state of the biopsy as assessed by the Molecular Microscope® Diagnostic (MMDx) System. Register at https://2020.ashi-hla.org/virtual-registration
Catch all of our Molecular Microscope® Diagnostic System (MMDx) presentations at ATC 2020
The 2020 American Transplant Congress (ATC) goes live on May 30, 2020. Don’t miss it! Molecular Microscope® Diagnostic System (MMDx) presentations at ATC 2020 Register at http://atcmeeting.org/registration
POSTER SESSION 3: Jr Faculty Case Reports: Lung Failure/Transplantation Presentation Number: 1419 Abstract Title: Immunologic Features and Therapeutic Challenges in Lung Transplantation for COPA Syndrome Associated Interstitial Lung Disease Link: to be updated when available
Dr. Philip F Halloran named as a laureate of the Czech Transplant Foundation Annual Award
Dr. Philip F Halloran was awarded the Czech Transplant Foundation Annual Award in Prague, Czechia, on 7 Nov 2019. The laureate is selected by the Czech Transplant Foundation’s Board of Trustees for discoveries with the greatest impact on transplantation medicine worldwide. Dr. Halloran was selected for the development of a new diagnostic tool, the Molecular Microscope® Diagnostic System (MMDx), developed by his team at the U of A in the Alerta Transplant Applied Genomics Centre (ATAGC). MMDx assesses disease and injury in organ transplant biopsies by using gene microarrays and machine learning/AI algorithms rather than histology, providing a precise and accurate basis for treatment decisions. Dr. Halloran accepted this award in a ceremony in the Karolinum, the seat of the Charles University and a national cultural monument of the Czech Republic. Charles University is one of Europe’s oldest universities, founded in 1348 by Emperor Charles IV, Holy Roman Emperor and King of Bohemia. The award ceremony began with Hussite Chorale ” Kdo jsou boží bojovníci” (“Who Are the Warriors of God”) created by Jan Čapek z Klatov in 15th Century, unofficial anthem of the Hussites and the modern Czech State. After the award and Dr. Halloran’s speech, there was a concert by violinist Václav Hudeček and pianist Lukáš Klánský playing compositions by Antonín Dvořák. Dr. Halloran was then interviewed on Czech national television. This award is particularly meaningful for Dr Halloran because he collaborated with the transplantation genetics researchers in Prague during his PhD studies in England at the very start of his research career.
Congratulations to Dr. Gunilla Einecke for receiving the Rudolf Pichlmayr Award
Our warmest congratulations go to our MMDx-Kidney collaborator, Dr. Gunilla Einecke of Hannover Medical School, Hannover, Germany, for receiving the Rudolf Pichlmayr Award for outstanding contributions to transplant medicine from the German Transplantation Society. What an outstanding achievement! Congratulations, Dr. Einecke!
ESOT Symposium Session: The Future of Transplant Care with the Molecular Microscope® Diagnostic System
Save the Date Sep 16 at 1PM How do you diagnose transplant injury precisely? Join us at ESOT 2019 as we explore a groundbreaking technology with the only advanced biopsy service that provides objective data for personalized transplant care. The Molecular Microscope Diagnostic System (MMDx) is now paving the way for the development of precision immunosuppression based on big data analysis by providing a new understanding of graft injury and rejection. MMDxSystemEvent details will be posted here: https://www.molecular-microscope.com/events/esot-2019
ATC 2019 Satellite Symposium: Transitioning from Empiric to Precision Medicine in Transplantation
Satellite Symposium: Transitioning from Empiric to Precision Medicine in Transplantation
Time & Location
Jun 03, 1:00 PM – 2:15 PM
Boston, MA, USA
Cutting edge technologies are paving the way for early detection of graft injury or rejection and charting a course for the development of precision immunosuppression based on big data. Join us as we explore a new patient path, an approach to treatment that includes strategies for risk stratification in pre-transplant testing as well as solutions for personalized post-transplant care. Guest Speakers: Peter Nickerson, MD | University of Manitoba – Winnipeg, Canada HLA Molecular Mismatch and DSA AssessmentJonathan Bromberg, MD, PhD | University of Maryland – Baltimore, MA Cell-free DNA for the Early Diagnosis of Rejection and Graft DysfunctionGaurav Gupta, MD | Virginia Commonwealth University – Richmond, VA Molecular Microscope® in Kidney Transplant Diagnostics
One Lambda hosting webinar featuring Dr. Philip Halloran on April 29 at 9 am PST
We’re excited to announce that One Lambda will host a webinar featuring Dr. Philip Halloran, who will present “The Molecular Microscope® Diagnostic System: Precision and Accuracy in Transplant Diagnostics.” Participants will have the opportunity to learn about the molecular phenotype of rejection and injury. Dr. Halloran will also discuss the unmet need for precision and accuracy in pathological biopsy assessment, review the applications of the actionable data generated in MMDx reports, and conclude with a live Q&A session. Register to earn CECs & invite a colleague to join! | Apr 29 | 9 AM PT | Register here: http://ow.ly/CeK350q0p82
2019 International Society for Heart and Lung Transplantation (ISHLT) Annual Meeting schedule of presentations by TSI/ATAGC and collaborators
Wednesday, April 3, 2019 Presenter: Michael Parkes Abstract Title: Molecular Analysis of Transbronchial and Mucosal Biopsies in Patients with CLAD Presentation number: 13 Time: 10:45 am Room: Pacifica 10-12
Friday, February 22, 2019 Arizona Biltmore, Phoenix, AZ, USA Session 3, option 3 8:35 AM Molecular Signals of Intragraft Rejection – Is INTERLUNG the Answer?
Session 3, option 2 9:35 AM Molecular Signals of Intragraft Rejection: Is INTERHEART true NORTH?
MOLPAT2019: Our collaborators from Austria, Czech Republic and Poland
TSI CEO and CSO Dr. Philip Halloran visited Prague for a conference dedicated to molecular pathology. The meeting featured many informative and interesting talks focusing on the application of molecular diagnostics and precise and accurate medicine in transplantation. Dr. Halloran is pictured with (from left to right) Georg Bohmig (Austria), Philip Halloran (Canada), Marek Myslak (Poland), and Ondrej Viklicky (Czech Republic). https://www.molpat2019.com/
Workshop on Molecular Pathology in Transplantation in Czech Republic, Prague on January 24 - 25, 2019
Dr. Halloran is travelling to Prague, Czech Republic to lecture at the Workshop on Molecular Pathology in Transplantation on January 24-25, 2019. The Preliminary Program can be viewed here: https://www.molpat2019.com/programme/
In September 2018, Dr. Philip F Halloran traveled to Paris, France for the 13th International Congress on Lung Transplantation to present two lectures: “The Molecular Landscape of Transbronchial Biopsies from Patients Diagnosed with CLAD” and “Molecular Microscope®”. Dr. Halloran then traveled to Warsaw and Gdansk in Poland to give a lecture at the Medical University of Warsaw (September 17, 2018) and the Medical University of Gdansk (September 19, 2018), “Molecular analysis of transplant biopsies: insights into mechanisms of disease”. He also led a workshop while in Warsaw, “Traditional Microscopic Evaluation vs. the Molecular Microscope®”. Szczecin, Poland was the next stop for the 13th Symposium of the Polish Transplantation Society to present the Plenary Lecture, “New Methods for Transplantation Diagnostics: The Molecular Microscope®” on September 20th. In October 2018, Dr. Halloran gave a lecture at NYU Langone Medicine Grand Rounds on October 10, 2018, “Molecular Analysis of Transplant Biopsies: Insights into Mechanisms of Disease”. He also attended the Transplant Institute Round Table, “The Molecular Microscope® Diagnostic System: developing and validating the assessment of kidney (MMDx-Kidney), heart (MMDx-Heart), and lung (MMDx-Lung) transplant biopsies”. Dr. Philip F Halloran traveled to Florida, USA on October 28, 2018 to give lectures on the Molecular Microscope® Diagnostic System. He presented at the Cleveland Clinic in Weston and Tampa Bay General Hospital in Tampa with lectures entitled “The Molecular Microscope® Diagnostic System (MMDx®): a new dimension for transplant biopsies”. On November 8th, Dr Halloran traveled to Baltimore, MD, USA to give a lecture entitled “The Molecular Microscope® Diagnostic System (MMDx®): a new dimension for transplant biopsies” at the inaugural Johns Hopkins Grand Rounds. Dr Philip Halloran presented at the Gairdner Symposium at the University of Alberta on November 15, 2018. Check out the link for details: https://www.ualberta.ca/medicine/about/events/u-of-a-gairdner-precision-health On November 16, 2018, Dr. Philip Halloran traveled to Zurich, Switzerland to lecture at the Borel-Staehelin Lecture – 12th Annual Symposium of the Transplant Center. His lecture was entitled “Molecular diagnostics in transplantation – lessons learned and added value.”
Five ways Phil Halloran is changing the lives of organ transplant patients around the world
UAlberta’s transplant research whiz recognized with 2018 J. Gordin Kaplan award, sciences category. By Kirsten Bauer on May 29, 2018 Philip Halloran’s research has contributed to the dramatic drop in transplantation failure rates―from 55 to just five per cent since the outset of his 40-year career. From the causes of organ rejection and moving on to diagnosis in treatment, the professor in the University of Alberta’s Division of Nephrology’s work has changed the lives of countless transplant patients around the world, making him a shoo-in for the U of A’s most prestigious research acknowledgment, the J. Gordin Kaplan Award for Excellence in Research in the sciences category. Named after the university’s first Vice-President, Research, the Kaplan recognizes and honours faculty members whose research contributions add significantly to our knowledge base, who are recognized nationally and internationally for their scholarly accomplishments and who set a standard of excellence for other U of A faculty, graduate and undergraduate students and the community-at-large. Halloran’s lifelong goal as a clinician-scientist is to see his research findings applied at the bedside, to improve the lives of people who have undergone a transplant. Here are a handful of his accomplishments to illustrate how he is advancing transplantation science.
1. He is disrupting diagnostic tools
Biopsy technology allows clinicians to determine the rejection stage of an organ after transplantation, but inaccurate measurements happen frequently. In order to improve accuracy of the testing, Halloran and his team have developed a diagnostic tool called MMDx (Molecular Microscope® Diagnostic System) which improves on existing biopsy methods for transplant organs by using gene chips to measure molecules instead of cells, making the test more precise and less invasive. MMDx was more than 30 years in the making, cost $35 million to develop and is ultimately a disruptive technology, explained Halloran. “This is a story of a team of researchers who believed in the value of something, even though it was paradigm-changing, and who worked diligently to establish scientific foundation in order to convince medical leaders in the field of its effectiveness and to get it into the hands of the public.”
2. He discovered why some organs are rejected
As a medical student, Halloran wanted to improve circumstances for the more than half of organ transplant patients at the time whose bodies rejected transplant. “There was a poor ability to understand the immune response to organ transplants and we couldn’t control rejections. There were desperate people, and a lot of lives were lost,” Halloran said. His determination eventually led to the discovery that both T cells (T cell-mediated rejection, TCMR) and antibodies (antibody-mediated rejection, “ABMR”) are some of the main culprits of organ rejection, with the help of the MMDx tool. Halloran is now recognized as defining ABMR as the major mechanism causing graft loss post-transplant. Although there is still more to learn about why rejection happens, Halloran’s ABMR discovery has led to research that will make more effective drug therapies available.
3. He is advancing anti-rejection drugs
Halloran led the development of a new companion drug called mycophenolate mofetil or Cellcept™ that improves survival rates and reduces side-effects of other drugs. According to Bruce Kaplan, professor of medicine at the Mayo Clinic in Scottsdale, Arizona, Halloran’s 2004 New England Journal of Medicine review on immunosuppressive drugs is now required reading for any transplant specialist in training. “I can say categorically, without bias, that Halloran is the most influential individual in transplantation over the past 25 years,” Kaplan said.
4. He founded the Alberta Transplant Applied Genomics Centre (ATAGC)
The ATAGC is an interdisciplinary research centre located at the U of A that focuses on understanding organ disease at the molecular level. The centre provides a means for international partners from across North America, Europe, Australia, and recently Asia to collaborate on research projects and to improve human health and scientific understanding of disease across multiple health disciplines.
5. His work is putting UAlberta at the epicentre of the international transplant map
The U of A recently rated sixth in the world in transplantation according to a new subjects ranking by the Center for World University Rankings. Halloran and his team have contributed significantly to the university climbing the transplant ranks. After winning the prestigious 2016 Prix Galien in Research, Halloran received a Doctor Honoris Causa from Paris Descartes University at the Musée d’Histoire de Médicine. Paris is considered to be an international home base of kidney transplant innovations, making Halloran’s induction a vote of confidence from some of the world’s leading transplant scientists. Halloran says there is now a very strong Paris-Edmonton connection, thanks to this prestigious recognition. “I feel that in honouring me they were honouring the distinguished history of the University of Alberta teams in organ transplantation.”
Congratulations to Phil Halloran on receiving University of Alberta's 2018 J. Gordin Kaplan Award for Excellence in Research
Full list of winners: https://www.ualberta.ca/vice-president-research/internal-honours-prizes/j-gordon-kaplan-laureates
Clinical trials show new U of A ‘molecular microscope’ system safer, more effective in heart and lung transplant biopsies
Research shows system requires less tissue samples and provides more precise readings.
April 24, 2018
Philip Halloran, the founder of the “molecular microscope” system for transplant biopsy, is presenting early clinical trial findings on the system today at the 2018 meeting of the International Society for Heart and Lung Transplantation. By LESLEY YOUNG
A transplant biopsy system that uses gene chips to read molecules is far safer and more effective than existing approaches used for heart transplant biopsies and is showing promising results for lung transplant biopsies, new University of Alberta-led research shows.
An international team of transplant specialists—including Philip Halloran, the founder of the “molecular microscope” system—presented early clinical trial findings of the system today at the 2018 meeting of the International Society for Heart and Lung Transplantation in Nice, France.
“Our research indicates that the molecular microscope system is more precise and accurate than conventional methods, which often involve extensive disagreement between doctors reading the biopsies, and therefore errors,” said Halloran, a U of A transplant physician and globally recognized leader in the field.
The method uses gene chips (similar to computer chips) to read the molecules in heart and lung transplant biopsies. In the molecular microscope system developed by the U of A’s Alberta Transplant Applied Genomics Centre (ATAGC) and investigators in North America, Europe and Australia, software converts the chip readings into diagnoses automatically.
Halloran said that the molecular microscope is a game changer in transplant medicine because it not only provides clinicians with insightful information for managing heart transplant rejection and treatment—which occurs in 150,000 patients worldwide every year—but also eliminates the confusion of unrecognized injury with rejection.
“Our findings suggest that, not infrequently, the current standard lacks the refinement to distinguish true rejection from other processes causing injury,” said Daniel Kim, U of A transplant cardiologist. “This implies that, at times, patients could be treated for a condition they don’t have. The molecular microscope’s ability to more accurately diagnose rejection, before structural damage has occurred in a patient’s heart, provides us with an essential tool in the evolution towards true precision medicine.”
The molecular microscope system is now being developed for lung transplant biopsies, with the goal of changing care for those patients as well.
“Reading small lung transplant biopsies with a microscope is challenging—much more so than other transplantable organs—and that makes diagnosing rejection that much more difficult and prone to error,” explained Kieran Halloran, assistant professor of medicine in the U of A’s Faculty of Medicine & Dentistry. “This molecular diagnostic system is at an earlier stage in lung compared to heart and certainly to kidney, but is showing promising results that it can see similar information. That potential is very exciting for lung transplant clinicians.”
He noted there is a huge unmet need for this type of precision medicine among lung transplant patients, who experience the shortest of all survival rates, often running into transplant trouble within five years.
“You can’t hit what you can’t see,” added Philip Halloran. “Transplant rejection can be going on and we are missing it. And more commonly, rejection is way overdiagnosed, and patients are experiencing treatment complications for a condition they didn’t have. Our system will change the approach to care.”
'Molecular microscope' system safer, more effective in heart and lung transplant biopsies
Research shows system requires less tissue samples and provides more precise readings UNIVERSITY OF ALBERTA FACULTY OF MEDICINE & DENTISTRY
A transplant biopsy system that uses gene chips to read molecules is far safer and more effective than existing approaches used for heart transplant biopsies and is showing promising results for lung transplant biopsies, new University of Alberta-led research shows. An international team of transplant specialists–including Philip Halloran, the founder of the “molecular microscope” system–presented early clinical trial findings of the system today at the 2018 meeting of the International Society for Heart and Lung Transplantation in Nice, France. “Our research indicates that the molecular microscope system is more precise and accurate than conventional methods, which often involve extensive disagreement between doctors reading the biopsies, and therefore errors,” said Halloran, a U of A transplant physician and globally recognized leader in the field. The method uses gene chips (similar to computer chips) to read the molecules in heart and lung transplant biopsies. In the molecular microscope system developed by the U of A’s Alberta Transplant Applied Genomics Centre (ATAGC) and investigators in North America, Europe and Australia, software converts the chip readings into diagnoses automatically. Halloran said that the molecular microscope is a game changer in transplant medicine because it not only provides clinicians with insightful information for managing heart transplant rejection and treatment–which occurs in 150,000 patients worldwide every year–but also eliminates the confusion of unrecognized injury with rejection. “Our findings suggest that, not infrequently, the current standard lacks the refinement to distinguish true rejection from other processes causing injury,” said Daniel Kim, U of A transplant cardiologist. “This implies that, at times, patients could be treated for a condition they don’t have. The molecular microscope’s ability to more accurately diagnose rejection, before structural damage has occurred in a patient’s heart, provides us with an essential tool in the evolution towards true precision medicine.” The molecular microscope system is now being developed for lung transplant biopsies, with the goal of changing care for those patients as well. “Reading small lung transplant biopsies with a microscope is challenging–much more so than other transplantable organs–and that makes diagnosing rejection that much more difficult and prone to error,” explained Kieran Halloran, assistant professor of medicine in the U of A’s Faculty of Medicine & Dentistry. “This molecular diagnostic system is at an earlier stage in lung compared to heart and certainly to kidney, but is showing promising results that it can see similar information. That potential is very exciting for lung transplant clinicians.” He noted there is a huge unmet need for this type of precision medicine among lung transplant patients, who experience the shortest of all survival rates, often running into transplant trouble within five years. “You can’t hit what you can’t see,” added Philip Halloran. “Transplant rejection can be going on and we are missing it. And more commonly, rejection is way overdiagnosed, and patients are experiencing treatment complications for a condition they didn’t have. Our system will change the approach to care.”
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Medscape Medical News: Molecular Diagnostics Pinpoint Heart Transplant Trouble
NICE, France — The molecular diagnosis of heart transplant biopsies is more precise than histologic analysis, and could become a new standard, results from the INTERHEART study (NCT02670408) show. “Agreement in histology is significant, but there are a lot of discrepancies,” said Philip Halloran, PhD, MD, from the Alberta Transplant Applied Genomics Centre at the University of Alberta in Edmonton. Molecular diagnosis is more objective and reproducible than histology, and provides new understanding of an organ’s reduced function in response to injury, he explained here at International Society for Heart and Lung Transplantation 2018 Scientific Sessions. Because increased diagnostic accuracy can eliminate confusion between transplant rejection and organ injury, treatment can be more precise and the administration of unnecessary immunosuppression drugs can be prevented, he said. Halloran and his colleagues assessed endomyocardial biopsy samples from 462 patients who had undergone heart transplantation at one of eight centers. Biopsies were performed a mean of 810 days after transplantation. Archetypal analysis, which assigns idealized extreme examples to compare all points analyzed, was conducted with Affymetrix microarrays. To compare molecular with histologic diagnoses, biopsies were assigned to one of three groups: no rejection, antibody-mediated rejection, or T-cell-mediated rejection. For molecular diagnosis, the researchers used a molecular diagnostic system developed for kidney transplant biopsies (Nat Rev Nephrol. 2016;12:534-548), which they found they could use for hearts (J Heart Lung Transplant. 2017;36:1192), as reported by Medscape Medical News.
Molecular Results Different From Histologic Finding
For the biopsies assigned to the no rejection group, the rate of agreement between molecular and histologic approaches was 82%. For those assigned to antibody-mediated rejection, the rate of agreement was 33%, and for those assigned to T-cell-mediated rejection, it was 36%. For biopsies with mixed results, the rate of agreement was 13%. The low rate of agreement between the two approaches is not a surprise. For 160 years, “we have looked down a microscope at a piece of tissue that’s been cut and stained with ancient dyes. We know that between two pathologists reading rejection, there’s only 28% agreement above random,” Halloran said. A previous study looked into histologic kappa values for concordance among pathologists (Transplantation. 2012;94:1172-1177). “There’s truth there, but there’s also a lot of noise, meaning errors,” he explained. In their investigation, Halloran and his colleagues found that molecular readings correlated with heart function, improved accuracy, and improved prediction of future failure. “Knowing what we know, we should be making diagnoses by looking at the messages from genes,” he asserted, adding that it’s time to embrace precision medicine.
Molecular Adds “Fourth Dimension” to Diagnosis
During the course of their investigation, the team found another dimension to molecular analysis, which they identified as “injury”. When they examined the histologic results, they found a high rate of error, particularly for biopsies assigned to T-cell-mediated rejection. These were, in fact, serious injuries that were not rejection but were confused with rejection, Halloran explained during his presentation of this second analysis of the data. “These were false-positives caused by injury, not rejection,” he reported. The histologic approach is not reliable and can lead to misdiagnosis, which could mean that patients are subjected to unnecessary treatment. “Antirejection drugs are heavy stuff. You don’t want those if you don’t need them,” said Halloran. “We need to include the dimension of injury in our diagnosis. This is something we can’t read with histology.”
Antirejection drugs are heavy stuff. You don’t want those if you don’t need them.
“This is significant progress,” said Andrew Fisher, PhD, from the Institute of Transplantation at Freeman Hospital in Newcastle Upon Tyne, United Kingdom. “Using an objective scientific approach instead of by eye, we can look at the molecular signature of a biopsy to make a more accurate diagnosis,” he told Medscape Medical News. In fact, a similar study looking at the molecular diagnosis of lung biopsy — conducted by a team led by Halloran’s son, Kieran Halloran, MD, also from the University of Alberta — will be presented at the meeting later this week. Halloran reports holding stock in Transcriptome Sciences. Fisher has disclosed no relevant financial relationships. International Society for Heart and Lung Transplantation (ISHLT) 2018 Scientific Sessions: Abstract 43, presented April 11, 2018; Abstract 178, presented April 12, 2018. Follow Medscape on Twitter @Medscape and Ingrid Hein @ingridhein
MMDx abstracts at the 2018 American Transplant Congress
Saturday, June 2, 2018Poster Presenter: Jeff Reeve Abstract Confirmation Number: 1976 Abstract Title: “Molecular Classifiers Can Outperform the Flawed Histologic “Gold Standard” on Which They Are Trained” Session: “Poster Session A: Biomarkers, Immune Monitoring and Outcomes” Date: Saturday, June 2, 2018 Location: Hall 4EF, Washington State Convention Center Publication/Poster Board Number: 56 Presentation Time: 5:30 pm – 7:30 pm Sunday, June 3, 2018Oral Presenter: Michael Parkes Abstract Confirmation Number: 1532 Abstract Title: “Molecular Phenotypes of Injury and Rejection in Lung Transplant Transbronchial Biopsies” Session: “Concurrent Session: Lung: From Allocation to Outcomes” Date: Sunday, June 3, 2018 Time: 2:30 pm – 4:00 pm PublicationNumber: 76 PresentationTime: 2:42 pm Oral Presenter: Michael Parkes AbstractConfirmationNumber: 932 Abstract Title: “T Cell-Mediated Rejection Poses Greater Risk to Graft Survival Than Antibody-Mediated Rejection in Heart Transplants” Session: “Concurrent Session: The Guest that NEVER leaves: Immunologic Challenges in Heart Transplantation” Date: Sunday, June 3, 2018 Time: 4:30 pm – 6:00 pm PublicationNumber: 170 PresentationTime: 5:18 pm Monday, June 4, 2018Oral Presenter: Gunilla Einecke Abstract Confirmation Number: 556 Abstract Title: “Predictors of Graft Survival at the Time of a Kidney Transplant Indication Biopsy” Session: “Concurrent Session: Kidney Complications: Late Graft Failure” Date: Monday, June 4, 2018 Time: 4:30 pm – 6:00 pm Publication Number: 322 Presentation Time: 5:42 pm Oral Presenter: Philip F Halloran Abstract Confirmation Number: 489 Abstract Title: “Inflammation in Scarred Areas (I-IFTA) is a Reflection of Parenchymal Injury (Response to Wounding) Not T Cell-Mediated Rejection” Session: “Concurrent Session: Kidney Chronic Antibody Mediated Rejection” Date: Monday, June 4, 2018 Time: 2:30 pm – 4:00 pm Publication Number: 210 Presentation Time: 3:42 pm Tuesday, June 5, 2018Oral Presenter: Philip F Halloran Abstract Confirmation Number: 1961 Abstract Title: “Validating Molecular Microscope Readings and Estimating Agreement with Histology” Session: “Concurrent Session: Kidney: Acute Cellular Rejection” Date: Tuesday, June 5, 2018 Time: 2:30 pm – 4:00 pm Publication Number: 455 Presentation Time: 3:06 pm Oral Presenter: Konrad Famulski Abstract Confirmation Number: 1150 Abstract Title: “Expression of the Senescence Marker P16/INK4A in Kidney Implantation Biopsies is Uniquely Associated with Poor Late Graft Function” Session: “Concurrent Session: Kidney Donor Selection / Management Issues – 2” Date: Tuesday, June 5, 2018 Time: 4:30 pm – 6:00 pm Publication Number: 521 Presentation Time: 5:42 pm
MMDx abstracts at the Transplantation Society 2018 International Congress
Monday, July 2, 2018 Abstract ID # 1581 Title: Molecular Assessment of Heart Transplant Biopsies: Emergence of the Injury Dimension Session Date and Time: 2018-07-02 from 09:45 to 11:15 Session Title: Heart Transplantation Order of Presentation: 1 Duration of Talk: 7 minutes presentation, followed by 3 minutes of Q&A Presenter: Dr. Philip F Halloran Wednesday, July 4, 2018Abstract ID # 1135 Title: In Kidney Allografts Inflammation in Scarred Areas is not a Reflection of Chronic Active T Cell-Mediated Rejection Session Date and Time: 2018-07-04 from 08:30 to 09:30 Session Title:Kidney Biopsy Order of Presentation: 1 Duration of Talk:7 minutes presentation, followed by 3 minutes of Q&A Presenter: Dr. Philip F Halloran
MMDx abstracts at the 2018 International Society for Heart and Lung Transplantation meeting
Session Title: PLENARY 1: Opening Plenary SessionSession Date/Time: Wednesday Apr 11, 2018 10:30 AM – 12:30 PMRoom Location: Apollon Presentation Number: 43Presentation Time: 11:30am – 11:45am Abstract Title: Molecular Diagnosis of Rejection Phenotypes in 889 Heart Transplant Biopsies: The INTERHEART Study Session Title: Poster Session 1: Pathology Session Date/Time: Wednesday Apr 11, 2018 6:15 PM – 7:15 PMRoom Location: Agora 2 Presentation Number: 766Poster Presentation Time: 6:15pm – 7:15pm Abstract Title: Histologic and Molecular Microscope Determinants of Graft Survival in the INTERHEART Study: The Greater Importance of T Cell-mediated Rejection vs. Antibody-mediated Rejection in Graft Loss Session Title: Poster Session 1: Pathology Session Date/Time: Wednesday Apr 11, 2018 6:15 PM – 7:15 PMRoom Location: Agora 2 Presentation Number: 767Poster Presentation Time: 6:15pm – 7:15pm Abstract Title: Validating the INTERHEART Classifiers for Molecular Diagnosis of Rejection in 558 New Endomyocardial Biopsies Session Title: ORAL SESSION 18: Mining the Tissue Biopsy: Molecular Signals of RejectionSession Date/Time: Thursday Apr 12, 2018 11:00 AM – 12:30 PMRoom Location: Hermes Presentation Number: 178Presentation Time: 11:30am – 11:45am Abstract Title: By Molecular Analysis, Many ISHLT Histologic Rejection Diagnoses Are Associated With Molecular Injury, Not Molecular Rejection
Showcasing MMDx at the European Society of Organ Transplantation Congress 2017
Transcriptome Sciences, Inc. (TSI) founder and CEO Dr. Phil Halloran delivered a featured plenary talk at the 2017 ESOT Congress on how the Molecular Microscope® system is used to understand disease states in organ transplants. Watch the video here.
PRNewswire: Thermo Fisher Scientific's One Lambda Brand Signs Exclusive Licensing Agreement with Transcriptome Sciences Inc. for access to Molecular Microscope Diagnostic System
One Lambda, a Thermo Fisher Scientific (NASDAQ:TMO) brand, has announced an exclusive licensing agreement with Transcriptome Sciences Inc. (TSI) for its Molecular Microscope® Diagnostic (MMDx) system. CLIA-licensed and CAP-accredited Kashi Clinical Laboratories, Inc. has adopted the MMDx technology in collaboration with Transcriptome Sciences Inc. and will be offering the service to process biopsy samples in the US. For more information on the MMDx test visit www.molecular-microscope.com. The full press release can be read at www.nasdaq.com.
A video montage recognizing Dr. Phil Halloran's contributions to the field of organ transplantation presented during the Doctor Honoris Causa ceremony at the Sorbonne in Paris.
TSI CEO and Founder Dr. Philip Halloran receives Doctor Honoris Causa award from Faculté de Médicine de University of Paris Descartes
Transcriptome Sciences Inc. (TSI) is proud to announce that its CEO and founder, Dr. Philip Halloran, received the award of Doctor Honoris Causa from Faculté de Médicine de University of Paris Descartes on December 14, 2016 in Paris, France. The ceremony took place in the historic Musee d’Histoire de Medicine, and the honorary doctorate from the Faculté de médecine de l’Université de Paris Descartes was presented by the Dean of Faculty of Medicine, Professeur Friedlander. Also in attendance were Prof. Denis Glotz, Dean Friedlander, Prof. Xavier Jouven, Prof. Alex Loupy, Prof. Carmen Lefaucheur, and Prof. Christophe Legendre. Many congratulations!
CEO Awarded with Prix Galien Award
CEO and Founder Dr. Philip Halloran has been honored with the prestigious 2016 Prix Galien Canada Research Award in Toronto, in recognition of his work in transplantation. “The Prix Galien is the most prestigious award in the field of Canadian pharmaceutical research and innovation. Referred to as the Nobel Prize of pharmaceutical research, it recognizes the efforts and achievements of pharmaceutical research and development. The Prix Galien Canada is organized by Innovation Life Canada, a non-profit organization whose mission is to celebrate Canadian innovation in the life sciences.” (Taken from http://innovativemedicines.ca/historic-honourees-celebrated-at-2016-health-research-foundation-research-awards-gala/, accessed November 23, 2016) Full article available here. Additional article here.
TSI & ATAGC Presentation Schedule
The Transcriptome Sciences team and their ATAGC partners will be well-represented at the 2017 American Transplant Congress in Chicago April 29-May 3. For a list of our talks and posters presented at the 2016 American Transplant Congress in Boston, please view or download the attached file. click here to open
TSI Launches New Website
Transcriptome Sciences Inc. (TSI) is proud to launch its new website, designed to be more interactive with the intention of staying connected to clinicians, investors, and scientists. Feel free to let us know what you think by sending us your comments at firstname.lastname@example.org