- Ph.D Biotechnology (National Centre for Cell Science, University of Pune, Maharashtra, India)
- M.Sc Microbiology (Sardar Patel University, Gujarat, India)
- B.Sc Microbiology (Sardar Patel University, Gujarat, India)
- May 2016- Till date: Scientist & DBT-Ramalingaswami Faculty Fellow, Rajiv Gandhi Centre for Biotechnology, Kerala, India.
- December 2014- April 2016: Research Associate, University of Pittsburgh School of Medicine, PA, USA
- January 2008- November 2014: Postdoctoral Associate, University of Pittsburgh School of Medicine, PA, USA.
- March 2006- September 2006: Visiting ResearchScholar, McGill University, Montreal, Canada
- June 2002- January 2003: Junior Research Fellow, Department of Microbiology, TheMaharaja Sayajirao University of Baroda, Gujarat, India.
- Ramalingaswami Re-entry Fellowship by DBT, India (2015)
- American Heart Association Postdoctoral Fellowship, USA (2013)
- Best Poster Award at University of PittsburghCell Biology Symposium, PA, USA (2012)
- Postdoctoral Fellow Travel Award to attend International Conference on Zebrafish Development and Genetics, Madison, WI, USA (2010)
- Best Poster Award at University of Pittsburgh Postdoctoral Symposium, PA, USA (2009)
- Doctoral Student Travel Award by Centre for Host-Parasite Interactions, Quebec, Canada (2006)
- Sabbatical Research Fellowship- Institute of Parasitology, McGill University, Montreal, Canada (2006)
- Best Poster Award at V Sir DorabjiTata Symposium on Leishmaniasis, Indian Institute of Science, Bangalore, India in collaboration with World- Health Organization and Tropical Disease Research group (2004)
- Senior Research Fellowship by CSIR, New Delhi, India (2005)
- Junior Research Fellowship and NET by CSIR, New Delhi, India (2003)
- Gold medal in B.Sc Microbiology at Sardar Patel University, Gujarat, India (1998)
Cells constantly acquire signals and nutrients from environment through cell surface receptors. The local density and itinerary of these receptorsdetermine the signaling and metabolic state of cells which ultimately dictate various cellular and physiological responses. Endocytosisis animportant process that modulatesthe density and local activity of these receptors.The focus of my research is to understand how the endocytic machineryis regulated to fine-tunecell signaling and metabolism and how this goes awry in cancer and cardiovascular diseases. To elucidate the mechanisms, we employmolecular and cell biological approaches integrated with gene-editing tools (CRISPRs and TALENs) and imaging techniques in cultured cells and model organisms.
1. Endocytic modulation of BMP signaling
Bone Morphogenetic Protein (BMP) receptors are agroup of TGF-β superfamily of signaling receptors that play crucial role in cell differentiation, embryonic development, cardiovascular development and adult tissue homeostasis.BMP receptors signal in response to a variety of bound BMP ligands and the signaling is dysregulatedin cardiovascular diseases and cancers. Our investigations show that endocytosis is pivotal for the fine tuning of BMP signaling. But how BMP receptors are sorted at the cell surface, endocytosed and transported through different intracellular compartments and how that lead to regulation of signaling events and ultimately to induction of a broad range of cellular responses remain elusive. We further seek to address these questions i) by identifying key players in the process of BMP receptor endocytosis and endosomal sorting ii) by decoding the molecular mechanisms of endosomal BMP signaling and iii) by delineating the mechanism of altered BMP receptor trafficking and dysregulatedsignaling in cardiovascular diseases and cancer. Ultimately, we hope to attain novel mechanistic insights into the molecular regulation of Bmp signaling in diseases and to the identification of potential therapeutic targets to Bmp signaling pathway and associated trafficking machinery.
2. Molecular mechanisms regulating endocytosis and intracellular trafficking of LDL receptor
Excess cholesterolis eliminated from the bloodstream through endocytosis of low density lipoproteins (LDL) bound LDL receptor (LDLR) from the cell surface followed bydissociation of LDL in lysosomes. Failure in LDLR sorting and endocytosis results in hypercholesterolemia or high blood cholesterolcondition and is the leading cause of coronary heart diseases and stroke. On the contrary, many aggressive tumors exhibit markedly enhanced cholesterol requirement for active proliferation and metastasis. These tumors heavily depend on LDLR endocytosis for their cholesterol uptake, making LDLR a promising metabolic target for cancer therapy. Endocytosis and intracellular trafficking of LDLR is thus very important and is coupled to stringent regulatory mechanisms that are not completely understood- viz; sterol dependent feed-back loops, metabolic and growth factor signaling pathways, proproteinconvertases, phosphorylation, ubiquitination- deubiquitination machinery etc. We are interested in deciphering these regulatory componentsthat impinge on endocytosis and intracellular trafficking of LDLR in healthy and disease states.
- Department of Science and Technology, Govt. of India: Extramural Research Grant (2018-2021)
- Department of Biotechnology, Govt. of India: Ramalingaswami Re-entry Fellowship (2016-2021)
- Ma L*, Umasankar PK*, Wrobel AG*, Lymar A, McCoy
AJ, Holkar SS, Jha A, Pradhan-Sundd T, Watkins SC, Owen DJ, Traub LM.
Transient Fcho1/2.Eps15/R.AP-2 Nanoclusters Prime the AP-2 Clathrin
Adaptor for Cargo Binding.Developmental Cell.
2016, 37(5):428-443. (* Co-first author)
[Previews: Prosser DC &Wendland B. DePFth Perception in Clathrin-Mediated Endocytosis. Developmental Cell. 2016, 37(5):387-388)].
- Jamdhade MD, Pawar H, Chavan S, Sathe G, Umasankar PK, Kiran MN, Dixit T, Keshava Prasad TS, Gowda H, Pandey A, Patole MS. Comprehensive proteomic analysis of glycosomes from Leishmaniadonovani. OMICS: A Journal of Integrative Biology. 2015, 19(3): 157-170.
- Umasankar PK, Ma L, Thieman JR, Jha A, Doray B, Watkins SC, Traub LM. A clathrin coat assembly role for the muniscin protein central linker revealed by TALEN- mediated gene editing. eLife. 2014, 10.7554/eLife.04137.
- Chakraborty S, Umasankar PK, Preston GM, Khandelwal P, Apodaca G, Watkins SC, Traub LM. A phosphotyrosine switch for cargo sequestration at clathrin-coated buds. Journal of Biological Chemistry. 2014, 289:17497-17514.
- Umasankar PK, Sanker S, Thieman JR, Chakraborty S, Wendland B, Tsang M, Traub LM. Distinct and separable activities of the endocyticclathrin-coat components Fcho1/2 and AP-2 in developmental patterning. Nature Cell Biology. 2012, 14:488-501. [News and views: Merrifield CJ. Fishing for clathrin-coated pit nucleators.Nature Cell Biology.2012, 14:452-454].
- Feng X, Feistel T, Buffalo C, McCormack A, Kruvand E, Rodriguez-Contreras D, Akopyants NS, Umasankar PK, David L, Jardim A, Beverley SM, Landfear SM. Remodeling of protein and mRNA expression in Leishmaniamexicana induced by deletion of glucose transporter genes. Molecular and Biochemical Parasitology. 2011, 175:39-48.
- Vathipadiekal V, Umasankar PK, Patole MS, Rao M. Molecular cloning, over expression, and activity studies of a peptidic HIV-1 protease inhibitor: designed synthetic gene to functional recombinant peptide. Peptides. 2010, 31:16-21.
- Edeling MA, Sanker S, Shima T, Umasankar PK, Höning S, Kim HY, Davidson LA, Watkins SC, Tsang M, Owen DJ, Traub LM. Structural requirements for PACSIN/Syndapin operation during zebrafish embryonic notochord development. PLoS One. 2009,4(12).
- Kulkarni MJ, Vinod VP, Umasankar PK, Patole MS, Rao M. Intact cell matrix-assisted laser desorption/ionization mass spectrometry as a tool to screen drugs in vivo for regulation of protein expression. Rapid Communications in Mass Spectrometry. 2006, 20:2769-2772.
- Umasankar PK, Jayakumar PC, Shouche YS, Patole MS. Molecular characterization of the hexokinase gene from Leishmania major. Journal of Parasitology. 2005, 91:1504-1509.