David Malkin , MD, FRCP(C), FAAP
The Hospital for Sick Children
Senior Staff Oncologist
Cancer Genetics Program
Genetics & Genome Biology
University of Toronto
Department of Paediatrics
Department of Medical Biophysics, School of Graduate Studies
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Dr. Malkin received his medical degree from the University of Toronto in 1984 and completed his residency in paediatrics and paediatric hematology/oncology at The Hospital for Sick Children in Toronto. He completed post-doctoral research training in molecular genetics at Massachusetts General Hospital, Harvard University, where he discovered the link between germline mutations on the p53 tumor suppressor gene and the Li-Fraumeni cancer susceptibility syndrome. Dr. Malkin returned to Canada to accept a faculty position at SickKids and University of Toronto.
Dr. Malkin is currently a clinician-scientist and paediatric oncologist in the Division of Hematology/Oncology and Director of the Cancer Genetics program at SickKids as well as a Senior Scientist in the Genetics & Genome Biology Program in the SickKids Research Institute. He is a Professor in the Departments of Paediatrics and Medical Biophysics in the Faculty of Medicine at the University of Toronto. Dr. Malkin has an active clinical oncology practice at the Hospital and both undergraduate and post-graduate teaching responsibilities there as well as at the University.
His research interests are closely integrated with his clinical field of expertise. Specifically, his research program focuses primarily on genetic mechanisms of childhood cancer susceptibility, and the genetic basis of childhood sarcomas (cancers of bone, muscle and other soft tissues). His research team was the first to demonstrate that highly variable regions of DNA, termed copy number variations, are found in excess in the blood of some people, both children and adults, at very high risk of developing cancer, and may represent the earliest genetic changes that ultimately lead to development of cancer. Recently, his work has focused on application of this genetic/genomic information to develop rational clinical surveillance and treatment guidelines for children and adults deemed at genetic ‘high risk’ for cancer. In his sarcoma work, Dr. Malkin has studied the molecular and cell biology pathways that are associated with the development and progression of these cancers, and has identified molecules that might represent viable targets for novel drug therapies.
Dr. Malkin has published over 150 peer-reviewed manuscripts and book chapters in the fields of cancer genetics and sarcoma biology. In addition, he has a long-standing interest in the ethical and medical issues raised by the creation of comprehensive biorepositories of tissues, blood and derivative biological samples from children with cancer. His work has been funded in part by the Canadian Cancer Society, Canadian Institutes for Health Research, Canada Foundation for Innovation, National Institutes of Health (US) and Department of Defense (US),Genome Canada, as well as other smaller agencies and foundations. He serves on several national and international cancer and research agencies and grant review panels and is the current chair of the Advisory Council on Research for the Canadian Cancer Society Research Institute (CCSRI), as well as the C17 Canadian Childhood Cancer and Blood Diseases Research Network.
Areas of Specialty:
Paediatric Oncology, Solid Tumours, Cancer Genetics
Clinical Care Activities
Dr. Malkin supervises a large active practice of children with solid tumors and familial cancer at SickKids and co-directs the Cancer Genetics Program, which now sees approximately 200 referrals annually. He is the institutional principle investigator on 8 clinical research or correlative biology studies of the Children's Oncology Group, with a particular focus on sarcomas and adrenocortical cancers.
Paediatric Haematology/Oncology Fellowship
The Hospital for Sick Children, 1987-07-01 to 1989-06-30
Post-Doctoral Research Fellowship
Massachusetts General Hospital, 1989-07-01 to 1992-01-01
- Role of p53 mutations in cancer predisposition phenotype known as Li-Fraumeni Syndrome.
- Role of VEGF (vascular endothelial growth factor) signaling in childhood sarcomas.
- Role of telomere maintenance in childhood brain tumours and cancer predisposition.
- Psychosocial impact of predictive genetic testing on children with cancer.
Dr. Malkin's research is closely integrated with his clinical field of expertise. Specifically, his research program focuses primarily on genetic mechanisms of childhood cancer susceptibility and the genetic basis of childhood sarcomas (cancers of bone, muscle and other soft tissues). His research team was the first to demonstrate that highly variable regions of DNA, termed copy number variations, are found in excess in the blood of individuals who harbor germline p53 mutations, both children and adults, at very high risk of developing cancer and may represent the earliest genetic changes that ultimately lead to development of cancer.
In addition, in collaboration with several national and international colleagues, he is studying the genome of children with specific types of brain tumors and sarcomas,using high-resolution genomic platforms, to identify novel genetic biomarkers of disease susceptibility and outcome. Recently, his work has focused on application of this genetic/genomic information to develop rational clinical surveillance and treatment guidelines for children and adults deemed at genetic ‘high risk’ for cancer. In his work on the common pediatric soft tissue tumor, rhabdomyosarcoma, Dr. Malkin has studied the molecular and cell biology pathways that are associated with the development and progression of these cancers, and has identified molecules that might represent viable targets for novel drug therapies.
Future Research Interests
- Expand functional and genotype:phenotype correlative studies of p53 alterations in Li-Fraumeni syndrome cancer associations.
- Explore role of VEGF signaling inhibition as novel target for therapeutic intervention in childhood sarcomas.
- Explore role of telomere:p53 interactions in childhood cancers.
- Pursue studies of ethical issues in childhood cancer predisposition syndromes.
Child Health Research Institute, Infrastructure for new Research Building. Rossant J, Malkin D, and 24 other co-applicants. Canada Foundation for Innovation [P.I. Rossant] [Malkin P.I. for Clinical Research Theme]
DNA Copy Number Variation in Li-Fraumeni Syndrome. Canadian Institutes for Health Research. Malkin D. (2009-2013) [P.I. Malkin]
Integrative Genomics for Health Research – Phase II. Canada Foundation for Innovation. Scherer S, Malkin D +8 other co-PIs. [P.I. Scherer]
Molecular Targeted Therapies of Childhood Choroid Plexus Carcinoma. Department of Defense (US). Gilbertson R, Malkin D, Guy K, Ellison D. [co-PIs: Gilbertson and Malkin]
Functional Oncogenomics for the Discovery of Cancer Drivers and Unique Subclasses (FOCUS). Ontario Research Fund – Global Leadership in Genomics and Life Sciences. Khokha R, Malkin D, Irwin M, Wood G, Stambolic V. [P.I. Khokha]
Molecular Determinants of Li-Fraumeni Syndrome-Associated Cancers. Canadian Institutes for Health Research. Malkin D [P.I. Malkin D]
The Canadian Pediatric Cancer Genome Consortium: Translating next-generation sequencing technologies into improved therapies for high-risk childhood cancer. CIHR-Genome Canada. Sorensen P, Malkin D, Taylor M, Huang A, Jabado N, Hawkins C, Sinnet D, Fernandez C. [P.I. Sorensen P]
- Dr. Harold E. Johns Award, Outstanding Research Scientist, Canadian Cancer Society (1997-2003)
- Award for Teaching Excellence, Paediatric Residents Lecture Series, The Hospital for Sick Children (1998, 2000)
- Elliot Osserman Award, Israel Cancer Research Fund (1998, 2002)
- Physician Researcher Award for Scientific Accomplishment, Department of Paediatrics, The Hospital for Sick Children, University of Toronto (2006)
- Man of Distinction Award, Israel Cancer Research Fund (2008)
Castel-Branco P, Zhang C, Lipman T, Fujitani M, Hansford L, Clarke I, Harley CB, Tressler R, Malkin D, Walker E, Kaplan D, Dirks P, Tabori U. Selective targeting of cancer stem cells by telomerase inhibition. Clin Cancer Res 17: 111-121, 2011.
Shlien A, Baskin B, Achatz MIW, Stavropoulos DJ, Nichols KE, Hudgins L, Morel CF, Adam MP, Zhukova N, Rotin L, Novokmet A, Druker H, Shago M, Ray PN, Hainaut P, Malkin D. A common molecular mechanism underlies two phenotypically distinct 17p13.1 microdeletion syndromes. Am J Human Genet 87(5): 631-642, 2010.
Xing J, Watkins WS, Shlien A, Walker E, Huff CD, Witherspoon DJ, Zhang Y, Simonson TS, Weiss RB, Malkin D, Woodward SR, Jorde LB. Toward a more Uniform Sampling of Human Genetic Diversity: A Survey of Worldwide Populations by High-density Genotyping. Genomics 96(4): 199-210, 2010
Durbin AD, Pasic I, Hannigan G, Malkin D. The oncogenic and growth-suppressive functions of the integrin-linked kinase are distinguished by JNK1 expression in human cancer cells. Cell Cycle 18; 9(10), 2010.
Tabori U, Shlien A, Baskin B, Levitt S, Ray P, Alon N, Hawkins C, Bouffet E, Pienkowska M, Laffay-Cousin L, Gozali A, Zhukova N, Shane L, Gonzalez I, Finlay J, Malkin D. TP53 Alterations determine clinical subgroups and survival of patients with choroid plexus tumors. J Clinical Oncology 28(12): 1995-2001, 2010.
Tabori U, Baskin B, Alon N, Taylor M, Ray PN, Bouffet E, Malkin D, Hawkins C. Universal poor survival in children with medulloblastoma harboring somatic TP53 mutations. Journal of Clinical Oncology 28(8): 1345-50, 2010
Durbin AD, Hannigan GE, Somers GR, Forrester M, Pienkowska M, Malkin D. JNK-1 determines the oncogenic or tumor suppressive activity of integrin-linked kinase (ILK) in rhabdomyosarcoma. J Clinical Investigation 2009 119(6): 1558-1570, 2009
Das B, Tsuchida R, Malkin D, Baruchel S, Yeger H. A hypoxia-driven ‘stemness switch’ is implicated in solid tumor progression and metastasis. Stem Cells May 10, 2008 [epub ahead of print]
Greenberg J, Somme S, Giercksky Russnes HE, Malkin D. The estrogen receptor pathway in rhabdomyosarcoma: a role for estrogen receptor-ß in proliferation and response to the antiestrogen 4’OH-Tamoxifen. Cancer Res 68 (9): 3476-3485, 2008.
Tabori U, Malkin D. Risk stratification in cancer predisposition syndromes: lessons learned from novel molecular developments in Li-Fraumeni syndrome. Cancer Res 68(7): 2053-2057, 2008.
Tsuchida R, Das B, Yeger H, Shibuya M, Baruchel S, Thorner PS, Malkin D. VEGF/Flt1 signaling regulates recovery of proliferative capacity of tumor side-population cells following exposure to cytotoxic chemotherapy in osteosarcoma. Oncogene March 10, 2008 [epub ahead of print].
Strahm B, Durbin AD, Sexsmith E, Malkin D. The CXCR4-SDF1alpha axis is a critical mediator of rhabdomyosarcoma metastatic signaling induced by bone marrow stroma. Clin Exp Metastasis 2008 25(1): 1-10.
Shlien A, Tabori U, Marshall C, Pienkowska M, Nanda S, Druker H, Novokmet A, Feuks L, Scherer S, Malkin D. Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome. Proc Natl Acad Sciences USA 105(32): 11264-11269, 2008
Greenberg J, Somme S, Giercksky Russnes HE, Malkin D. The Estrogen Receptor Pathway in Rhabdomyosarcoma: A Role for Estrogen Receptor-ß in Proliferation and Response to the Antiestrogen 4’OH-Tamoxifen. Cancer Res 68 (9): 3476-3485, 2008.
Tabori U, Lees J, Druker H, Nanda S, Malkin D. Telomere shortening and early cancer development in Li-Fraumeni syndrome. Cancer Research 2007 67(4): 1415-1418.[
Tabori U, Lees J, Druker H, Nanda S, Malkin D. Telomere shortening and early cancer development in Li-Fraumeni syndrome. Cancer Research 2007 67(4): 1415-1418.[Featured Article].
West AN, Neale GA, Pounds S, Figueredo BC, Galindo CR, Pianovski MAD, Filho AGO, Malkin D, Lalli E, Ribeiro R, Zambetti GP. Gene expression profiling of childhood adrenocortical tumors. Cancer Research 2007: 67(2): 600-608.
Tabori U, Ma J, Carter M, Zielenska M, Rutka J, Bouffet E, Bartels U, Malkin D, Hawkins C. hTERT expression predicts progression and survival in pediatric intracranial ependymoma. Journal of Clinical Oncology 2006: 24(10): 1522-1528.
Tabori U, Vukovic B, Zielenska M, Braude I, Hawkins C, Rutka J, Bouffet E, Squire J, Malkin D. Telomerase activity and telomere length in the biological behaviour of pediatric low grade gliomas. Neoplasia 2006: 8(2): 136-142. [Featured Article]
Strahm B, Malkin D. Hereditary cancer predisposition in children: molecular basis and clinical implications. International J Cancer 2006: 119: 2001-2006.
Ganjavi H, Gee M, Narendran A, Parkinson N, Krishnamoorthy M, Freedman MH, Malkin D. Adenovirus-mediated p53 gene therapy in osteosarcoma cell lines: sensitization to cisplatin and doxorubicin. Cancer Gene Therapy 2005. 13(4): 415-419.
Barlow JW, Wiley JC, Mous M, Narendran A, Gee MFW, Goldberg M, Sexsmith E, Malkin D. Differentiation of rhabdomyosarcoma cell lines using retinoic acid. Pediatric Blood Cancer 2006; 47(6):773-784
Das B, Yeger H, Tsuchida R, Torkin R, Gee MFW, Malkin D, Baruchel S. A hypoxia-driven VEGF/Flt1 autocrine loop interacts with HIF-1alpha through MAPK/ERK1/2 pathway in neuroblastoma. Cancer Research 2005; 65(16) 7267-7275.
Gee MF, Eichler-Jonsson C, Das B, Tsuchida R, Baruchel S, Malkin D. Vascular endothelial growth factor acts in an autocrine manner in rhabdomyosarcoma cell lines and can be inhibited with all-Trans-retinoic acid. Oncogene 2005; 24(54): 8025-8037.
Ganjavi H, Gee M, Narendran A, Freedman MH, Malkin D. Adenovirus-mediated p53 gene in soft tissue sarcoma cell lines: sensitisation to cisplatin and adriamycin. Cancer Gene Therapy 2005; 12(4):397-406.