2025 Gairdner Early Career Investigator Competition

Dr. Daniel De Carvalho is a Senior Scientist at the Princess Margaret Cancer Centre, University Health Network, and a Full Professor in the Department of Medical Biophysics at the University of Toronto. He is also the co-founder and CSO of Adela. His research focuses on the role of epigenetic modifications, particularly DNA methylation, in cancer development, therapy, and early detection. He has made significant contributions to understanding how epigenetic changes influence tumor behavior and immune recognition, leading to the development of innovative therapeutic strategies that integrate epigenetic therapy with immunotherapy. His work has also been instrumental in advancing cfDNA methylation technologies for detecting, classifying, and monitoring tumors through liquid biopsy.

Since establishing his independent research program in 2012, Dr. De Carvalho has been widely recognized for his contributions to cancer research. He has received numerous honors, including the Bernard and Francine Dorval Prize, the AACR-Waun Ki Hong Award for Translational Cancer Research, a Canada Research Chair, and election to the Royal Society of Canada’s College of New Scholars, Artists and Scientists. His research continues to drive advancements in cancer epigenetics, with the goal of improving early detection and developing more effective treatment strategies.

Dr. Iva Greenwald received her B.S. from Cornell in 1977, her Ph.D. from MIT in 1982, and conducted postdoctoral research at the MRC Laboratory of Molecular Biology from 1983-1986.  She then joined the faculty of Princeton University (1986-1993) and moved to the Dept. of Biochemistry and Molecular Biophysics on the medical campus of Columbia University in 1993. Since 2016, Dr. Greenwald has had a primary appointment in the Dept. of Biological Sciences on the Morningside campus of Columbia. Her honors include election to the National Academy of Sciences (USA) in 2005.

Dr. Greenwald's work on the conserved LIN-12/Notch signaling system falls into two partially overlapping phases. In the first phase, she identified and elucidated the fundamental properties of the system, including (i) its role as a binary switch for regulating alternative cell fate decisions, (ii) its sequence as a transmembrane protein and its function in signal-reception, (iii) its archetypal role and mode of action in the feedback amplification of intercellular signals, (iv) the discovery of the intramembrane protease Presenilin as a core component of the Notch signaling system, and characterization of other core components, and (v) together with Dr. Gary Struhl, the novel “cleavage and nuclear import” mechanism of signal transduction and for Presenilin in executing the transmembrane cleavage event. In the second phase, she focused on identifying (i) new regulators of LIN-12/Notch activity, trafficking and stability, such as the tumor suppressor SEL-10/FBXW7, (ii) target genes and genetic circuitry, and (iii) how LIN-12/Notch and other signals are integrated during development.

Paul received both his B.S. and Ph.D. from U.C. Berkeley in Physiology and carried out post-doctoral work at U.C. Berkeley and U.C. Irvine in the areas of epithelial biology, ion channel biophysics and immunology. Following postdoctoral work, Paul joined Aurora Biosciences in 1996, a San Diego Company whose founders included Nobel Prize Laureate Roger Tsien. Paul began working on cystic fibrosis (CF) and pain while at Aurora and played an important role in establishing the collaboration with the Cystic Fibrosis Foundation.  

When Vertex acquired Aurora in 2001, Paul was responsible for integrating Aurora’s research into Vertex. From 2003 to 2022, Paul served as Site Head for the Vertex San Diego research site. During that time, the San Diego team discovered over a dozen clinical candidates, including the first CFTR modulators for CF to enter clinical studies. Five of these compounds, ivacaftor, lumacaftor, tezacaftor, elexacaftor, and vanzacaftor are now approved medicines to treat the underlying cause of cystic fibrosis and could treat up to 90% of people with CF.  

Paul’s work, and leadership of his team, has been recognized externally. He received the Warren Alpert Prize and was a 2022 Shaw Prize in Life Sciences and Medicine recipient. In 2023, Paul received the Wiley Prize in Biomedical Sciences and in 2024 Paul and his Vertex colleagues were recognized with the 2024 Breakthrough Prize in Life Sciences for “developing life-transforming drug combinations that repair the defective chloride channel protein in patients with cystic fibrosis.

Dr. Gary Struhl received his B.S. and M.S. from MIT (1976), and conducted his Ph.D. and postdoctoral research, respectively, at the MRC Laboratory of Molecular Biology (1976-1982), and Harvard University (1982-1985). He is a professor of Genetics and Development at Columbia University (1985-present), and an elected member of the USA National Academy of Science (2008).

Dr. Struhl studies how growth and patterning are organized during animal development, from global gradients that govern body patterns to secreted morphogens that organize the development of individual organs, to local communication between cells that controls their fates and polarity. In the 1990’s, together with Dr. Iva Greenwald, he discovered that the intracellular domain of Notch has intrinsic and constitutive transducing activity and provided the first evidence that Notch is a receptor that acts via the regulated nuclear access of its cytosolic domain. He then developed an in vivo, chimeric protein approach to establish (i) that the Notch intracellular domain is a membrane-tethered transcriptional activator, (ii) that release and nuclear import of this domain depends on cleavage of the tether by the intramembrane protease Presenilin (with Dr. Greenwald), (iii) that ligand converts the tether into a substrate for Presenilin by inducing the cleavage and shedding of the receptor ectodomain, and (iv) that ligand triggers the requisite ectodomain cleavage by exerting mechanical force on the receptor. Taken together, these findings elucidate a causal chain of events that define the basic mechanism of Notch signal transduction and establish this mechanism as a new paradigm of intercellular communication.

Dr. Michael Welsh obtained an MD and completed an internal medicine residency at the University of Iowa.  He trained in pulmonary medicine and research at the University of California, San Francisco and University of Texas, Houston.  He then joined the University of Iowa where he is Professor of Internal Medicine, Molecular Physiology and Biophysics, and Neurology.  He was an HHMI Investigator from 1989-2024.  He directs the Cystic Fibrosis Research Center and Pappajohn Biomedical Institute.  

Dr. Welsh’s clinical activities focused on pulmonary diseases.  He cared for people with cystic fibrosis on the wards and in the clinics.  That experience and the lack of effective treatments influenced his decision to pursue the fundamental defects causing cystic fibrosis lung disease with the hope of improving the lives of people suffering from cystic fibrosis.

He has trained many physicians and scientists and received the Distinguished Mentor Award, University of Iowa Carver College of Medicine.  Dr. Welsh served as president of the American Society for Clinical Investigation and the Association of American Physicians.  He was elected to the National Academy of Medicine, American Academy of Arts and Sciences, and National Academy of Sciences.  He received the Gordon Wilson Medal, Walter Cannon Award, Steven Beering Award, Warren Alpert Foundation Prize, Kober Medal, Shaw Prize in Life Science and Medicine, Wiley Prize, and Switzer Prize.