THE HESS LAB
HEAL THYSELF: DEVELOPING REGENERATIVE THERAPIES FOR DIABETES AND ITS CARDIOVASCULAR COMPLICATIONS
The human body possesses tremendous capacity to heal itself! Tissue specific stem cells are found within every organ and possess the capacity to replace damaged cells or secrete signals that coordinate complex tissue repair and regenerative processes.
We envision stem cells as ‘conductors of the orchestra’ that direct the myriad of cells and events involved in the regenerative response. However, during chronic diseases such as diabetes, relentless damage exhausts the stem cell pool, leading to progressive disability due to the development of cardiovascular disease.
In the Hess laboratory, we aim to understand the mechanisms by which distinct stem cell coordinate islet and blood vessel regeneration. The overarching goal of our research program is the use of post-natal stem cells for the development of new and improved therapies for diabetes and its related cardiovascular complications.
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We specialize in isolating and studying various stem cell lineages, including hematopoietic, endothelial, and mesenchymal cells. Through high-speed fluorescence-activated cell sorting and a deep understanding of conserved stem cell functions, we are expanding the boundaries of what is possible in regenerative medicine.
OUR WORK
Our multidisciplinary research program addresses several barriers in the field of regenerative medicine for diabetes:
To generate stem cell-based biotherapeutics that suppress autoimmunity and stimulate islet formation.
To develop translational bioengineering technologies that promote the survival/regenerative function of transplanted stem cell lineages required for blood vessel regeneration.
To discover novel pharmaceutical agents for the reversal of vascular regenerative stem cell exhaustion in individuals with diabetes.
Harnessing the power of stem cells for islet and blood vessel regeneration, we strive to improve the health and longevity of individuals living with diabetes.
CURRENT PROJECTS
This section provides an overview of our current projects. Please note that some of these initiatives are collaborative efforts involving researchers not only at Western University but also at The University of Toronto. We believe in the power of teamwork and interdisciplinary cooperation to drive innovation in stem cell research.
Islet regeneration and replacement strategies
These projects aim to restore beta cell function and recapitulate insulin homeostasis in diabetic mouse models. Strategies include the use of mesenchymal stem cell (MSC)-secreted proteins to stimulate islet regeneration in situ and using lineage tracing to determine the mechanisms of regeneration. We are also elucidating the effects of MSC-secreted proteins on hESC-derived pancreatic progenitor cell differentiation and function.
Bioengineering blood vessels
In collaboration with bioengineer Lauren Flynn, we seek to characterize the ability of human decellularized adipose tissue hydrogels to (1) act as a culture platform to support the pro-angiogenic function of MSC and endothelial colony forming cells in co-culture, and (2) improve cell survival and retention and hindlimb reperfusion following implantation in vivo.
Vascular regenerative cell exhaustion
We have developed a novel flow cytometry assay to quantify vascular regenerative cell content based on the detection of circulating
progenitor cell subsets with high aldehyde dehydrogenase-activity. Using this unique platform, we have established that people with T2D and/or obesity exhibit the depletion and dysfunction of ALDHhi progenitor cells and monocytes with vessel regenerative function. We refer to this imbalance as vascular regenerative cell exhaustion.
NEW!!
Vascular Regenerative Cell Deficiencies in South Asian Adults. (2024)
Aishwarya Krishnaraj, Ehab Bakbak, Hwee Teoh, Yi Pan, Irene N. Firoz, Arjun K. Pandey, Daniella C. Terenzi, Raj Verma, Basel Bari, Asaad I. Bakbak, Shakkeela Padanilathu Kunjummar, Bobby Yanagawa, Kim A. Connelly, C. David Mazer, Ori D. Rotstein, Adrian Quan, Deepak L. Bhatt, Darren K. McGuire, David A. Hess, and Subodh Verma. (2024) Journal of the American College of Cardiology 83(7): 755–769.
As featured in CBC
Bone marrow–derived stem cells initiate pancreatic regeneration. (2003)
Hess D, Li L, Martin M, Sakano S, Hill D, Strutt B, Thyssen S, Gray DA, and Bhatia M. Bone marrow-derived stem cells initiate pancreatic regeneration. (2003) Nature Biotechnology 21(7): 763-770.
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LeClerc CJ, Cooper TT, Bell, GI, Lajoie GA, Flynn LE, Hess DA. Decellularized adipose tissue scaffolds guide hematopoietic differentiation and stimulate vascular regeneration in a hindlimb ischemia model. (2021) Biomaterials 274:120867. Epub May 8.
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Hess DA, Terenzi DC, Trac JZ, Quan A, Mason T, Al-Omran M, Bhatt DL, Dhingra N, Rotstein OD, Leiter LA, Zinman B, Sabongui S, Yan AT, Teoh H, Mazer CD, Connelly KA, Verma S. SGLT2 inhibition with empagliflozin increases circulating provascular progenitor cells in people with type 2 diabetes mellitus. (2019) Cell Metabolism, 30(4):609-613.
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High aldehyde dehydrogenase and expression of cancer stem cell markers. (2009)
Croker AK, Goodale D, Chu J, Postenka C, Hedley BD, Hess DA, Allan AL. High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. (2009) Journal of Cellular and Molecular Medicine 13(8B): 2236-2252
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Hess DA, Meyerrose TE, Wirthlin L, Craft TP, Herrbrich PE, Creer MH, Nolta JA. Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity. (2004) Blood 104(6): 1648-1655.
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Qadura M, Terenzi DC, Verma S, Al-Omran M, Hess DA. Cell therapy for critical limb ischemia: An integrated review of preclinical and clinical studies. (2018) Stem Cells, 36(2):161-171.
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Hess DA, Wirthlin L, Craft TP, Herrbrich PE, Hohm SA, Lahey R, Eades WC, Creer MH, Nolta JA. Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells. (2006) Blood 107(5): 2162-2169.
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Vascular repair and regeneration in cardiometabolic diseases. (2022)
Hess DA, Verma S, Bhatt D, Bakbak E, Terenzi DC, Puar P, Cosentino F. Vascular repair and regeneration in cardiometabolic diseases. (2022) European Heart Journal 43(6): 450-459.
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PUBLICATIONS
COURSES
4930F at Western University, undergraduate
Interdisciplinary Thinking and Research Literacy in Medical Sciences
Dr. Hess delivers a guest lecture on stem cells and diabetes. This capstone course investigates selected topics in medical science research. Students learn about human diseases/conditions that impact health systems (e.g., diabetes, cancer, neurodegenerative disease, etc.) from disciplinary lenses and engage in discussions about the academic publication process. Students develop research literacy, critical and interdisciplinary thinking, and communication skills.
9553 at Western University, graduate
Translational Research (Bench to Bedside)
Dr. Hess is a regular lecturer for this course. The objective of this course is to familiarize students with the approaches and issues associated with taking a basic science discovery through to effective therapeutic use in patient populations. An additional objective is to expand the scope of students' understanding of how their graduate research project fits into the ‘bigger picture' of the advancement of science and medicine.
4520B at Western University, undergraduate
Stem Cell Biology and Regenerative Medicine
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Coordinated and managed by Dr. Hess, this course explores fundamental concepts in regenerative medicine, including stem cell biology, and focuses on the physiology and pathophysiology of hematopoiesis and cancer development, blood vessel formation for tissue repair, and cellular transplantation for regenerative therapies.
4980 at Western University, undergraduate
Seminar and Research Project (4th year thesis)
A major laboratory project in Physiology or Pharmacology, which emphasizes experimental design, instrumentation, collection and analysis of data and communication of experimental results by oral, poster and written presentations. Students will select the physiology or pharmacology project from a list provided by the department and be matched to a supervisor.
TEAM
Our Current Lab Members
Principal Investigator
David A. Hess
Sheldon H. Weinstein Chair in Diabetes Research, Schulich School of Medicine
Scientist, Molecular Medicine Research Labs, Robarts Research Institute
Professor, Physiology & Pharmacology, Western University
Adjunct Professor, Pharmacology & Toxicology, University of Toronto
PhD Pharmacology & Toxicology, Western University
Former Trainees
David Putman
PhD Physiology & Pharmacology
MD University of Toronto
Ayesh Seneviratne
MSc Physiology & Pharmacology
MD/PhD at University of Toronto
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Miljan Kuljanin
PhD Biocheistry (co-supervised by Dr. Gilles Lajoie)
PDF at Harvard University
Joban Dhillon
MSc Physiology & Pharmacology (co-supervised by Dr. Lauren Flynn)
MD McGill University
Ahmed Shah
MSc Physiology & Pharmacology
(co-supervised by Dr. Cheryle Seguin)
MD University of Toronto
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Stephen Sherman
PhD Physiology & Pharmacology
PDF at Harvard University
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Tyler Cooper
PhD Physiology & Pharmacology
PDF at Western University
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Ruth Elgamal
MSc Physiology & Pharmacology
PhD candidate at the University of California, San Diego
Chris LeClerc
MEng Biomedical Engineering
(co-supervised by Dr. Lauren Flynn)
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Brianna Ananthan
MSc Physiology & Pharmacology
MD Candidate at Western University
Nazihah Rasiwala
MSc Physiology & Pharmacology
Daniella Terenzi
PhD Integrated Medical Sciences, University of Toronto
MD at University College Dublin
Justin Trac
MSc Pharmacology & Toxicology, University of Toronto
DDS at UofT
Kushvir Saini
BMSc Physiology & Pharmacology
MD Candidate at University of Toronto
Arianna He
BMSc Physiology & Pharmacology
Ehab Bakbak
PhD (co-supervised by Dr. Subodh Verma at UofT)
MD Candidate at University of Queensland