Joydeep Mukherjee, PhD
Research Interest: Understanding the role of altered cell metabolism and its effect on glioma microenvironment for therapeutic intervention
Almost 80% of Lower-grade glioma (LGG) contain mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Although various functional roles of mutant IDH1 enzyme has been explored so far but none of them showed its potential link in telomere regulation. Telomeres are a cap like structure at the DNA ends of chromosomes that are usually maintained by TERT, the catalytic component of telomerase. Lower-grade astrocytomas (grade 2 and 3 astrocytomas, LGA), however, use an alternative, homologous recombination (HR)-based mechanism to elongate telomeres. In LGA, loss of function mutations in the chromatin remodeler ATRX, and gain of function mutations in IDH1 are uniformly associated with the alternative lengthening of telomere (ALT) phenotype. While ATRX loss is known to contribute to increased HR at telomeric sequences, the contribution of mutant IDH1 to ALT is neither proven nor understood. We recently showed that mutant IDH1 expression initiates telomeric dysfunction and alters DNA repair pathway preference at telomeres which not only have implications for our understating of the ALT phenotype, but also for the therapy of ALT tumors which is my long-term goal.
2010: Post-doctoral training, Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, University of Toronto
2004: Ph.D., Brain Tumor Immunology, Institute of Post Graduate Medical Education and Research (IPGME&R), University of Calcutta
2000: M.Sc., Master of Science in Zoology with specialization in Advance Cytology and Genetics, University of Calcutta
1998: B.Sc., Bachelor of Science (Hons.) in Zoology, University of Calcutta
2017: Adult Basic Research Abstract Award, Society of Neuro-oncology, USA
2017: Andrew Parsa Young Investigator Award, Society of Neuro-oncology, USA
2008: Exceptional Research Trainee Award, The Hospital for Sick Children Research Institute, Toronto, ON, Canada
2008-2010: Ontario Post-Doctoral Fellowship, Ministry of Research and Innovation, Government of Ontario
2007: Young Investigator Award from Pediatric Brain Tumor Foundation, USA (PBTF)
2007-2008: University of Toronto, Post-Graduate Medical Education Research Grant Award, Edward Christie Stevens Fellowship
2007-2009: American Brain Tumor Association (ABTA) Basic Research Fellowship for two-year for basic brain tumor research
2006-2007: Young Investigator Award, The Children’s Tumor Foundation, New York, N.Y. 10005
2006-2007: University of Toronto, Post-Graduate Medical Education Research Grant Award, Edward Christie Stevens Fellowship and Heidi Sternbach Scholarship
Mutant IDH1 co-operates with ATRX loss to drive the alternative lengthening of telomere (ALT) phenotype in glioma
Mukherjee J, Johannessen TC, Ohba S, Chow TT, Jones L, Pandita A, Pieper RO.
Cancer Res. 2018 Jun 1;78(11):2966-2977.
PKM2 uses control of HuR localization to regulate p27 and cell cycle progression in human glioblastoma cells
Mukherjee J, Ohba S, See WL, Phillips JJ, Molinaro AM, Pieper RO.
International J Cancer. 2016 Jul 1;139(1):99-111.
Changes in pyruvate metabolism detected by magnetic resonance imaging are linked to DNA damage and serve as a sensor of temozolomide response in glioblastoma cells
Park I*, Mukherjee J,* Ito M, Chaumeil MM, Jalbert LE, Gaensler K, Ronen SM, Nelson SJ, Pieper RO.
Cancer Research. 2014 Dec 1;74(23):7115-24. * Both authors contributed equally to this work.
Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme
Wolf A, Agnihotri S, Micallef J, Mukherjee J, Sabha N, Cairns R, Hawkins C, Guha A.
Journal of Experimental Medicine, 2011 Feb 14; 208(2): 313-26.
Loss of collapsin response mediator Protein1, as detected by iTRAQ analysis, promotes invasion of human gliomas expressing mutant EGFRvIII
Mukherjee J, DeSouza LV, Micallef J, Karim Z, Croul S, Siu KW, Guha A.
Cancer Research. 2009 Nov 15;69(22):8545-54.
Human schwannomas express activated platelet-derived growth factor receptors and c-kit and are growth inhibited by Gleevec (Imatinib Mesylate).
Mukherjee J, Kamnasaran D, Balasubramaniam A, Radovanovic I, Zadeh G, Kiehl TR, Guha A.
Cancer Research. 2009 Jun 15;69 (12):5099-107.