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Indiana University School of Medicine
Indiana University School of Medicine

Sankar Lab

The research lab of Uma Sankar, PhD uses global and conditional knockout mouse models, biochemical, molecular biology and cell biology techniques as well as pharmacological inhibitors to investigate the mechanisms by which members of the Calcium/calmodulin dependent protein kinase (CaMK) signaling cascade, CaMKK2 along with its downstream kinases AMPK, CaMKI and CaMKIV; regulate the fate and function of bone marrow-derived mesenchymal stem cells, osteoblasts and osteoclasts.

Active Research

This lab team is pursuing in vivo translational studies investigating CaMKK2 inhibition as a bone anabolic strategy in accelerating fracture healing and combating age- and cancer-associated osteoporosis as well as osteoarthritis. Further, CaMKK2 is over-expressed in prostate cancer, and recent studies identify it to be a direct target of androgen receptor. Investigators here are interested in identifying the effects of CaMKK2 inhibition in prostate cancer-associated bone metastasis as well as establishing the identity of its downstream targets in prostate cancer as well as bone cells.

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Research Funding

The Sankar laboratory is funded by the American Cancer Society and the NIH.

2013, American Cancer Society Research Scholar –Sankar

2015, National Institutes of Health R01

Recent Publications: Role of CaMKK2 in Bone Cell Biology

Role of CaMKK2 in bone cell biology: Anabolic therapies in the treatment of osteoporosis are largely underdeveloped and form the highest clinical need. This lab team recently identified CaMKK2 as a novel regulator of osteoblast and osteoclast biology. Using a global knockout of this kinase as well as a selective pharmacological inhibitor, investigators identified a significant anabolic and anti-catabolic bone phenotype in mice when CaMKK2 expression is lost or its activity is inhibited. These studies are highly significant as anabolic therapies that can replace lost bone while inhibiting the catabolic arm of bone remodeling are of utmost clinical relevance. This is a recently developed project and two manuscripts are currently in review.

Sankar U, Pritchard ZJ, Voor MJ. Micro-computed tomography assisted distal femur metaphyseal blunt punch compression for determining trabecular bone strength in mice. J Biomech. 2016 May 3;49(7):1233-7 PMID: 26947030.

Recent Publications: Osteoclast Biology

Osteoclast biology: My contributions to this field include the identification of the mechanism by which RANKL co-ordinates cell cycle exit during differentiation by osteoclast progenitors and the role of Microphthalmia transcription factor in osteoclast biology.

Sharma S. M., Ostrowski M. C and Sankar U. 2009. Defective Co-activator Recruitment in Osteoclasts from Microphthalmia-Oak Ridge Mutant Mice. Journal of Cellular Physiology: 220: 230-237; PMID: 19288495.

Recent Publications: Role of CaMKIV and its Targets in Stem Cell Biology

Role of CaMKIV and its targets in stem cell biology:  Using genetic knockout mouse models, we reported a role for CaMKIV in the control of hematopoietic stem cell (HSC) proliferation and survival.  A subsequent microarray screen for downstream targets identified Growth Factor erv1-like (Gfer) to be significantly down-regulated in Camk4-/- HSCs.  Using loss and gain-of-function experiments we found a key role for Gfer in HSC proliferation, similar to that of CaMKIV. Further investigations have revealed that Gfer regulates mitochondrial fission-fusion dynamics in embryonic stem cells.  A manuscript showing the mechanism by which Gfer regulates the mitochondrial fission GTPase Drp1 is under review.

Teng, E.C., Todd, L.R., Ribar, T.J., Lento, W., Dimascio,L., Means, A.R. and Sankar, U. 2011. Gfer Inhibits Jab1-Mediated Degradation of p27kip1 to Restrict Proliferation of Hematopoietic Stem Cells. Molecular Biology of the Cell: 22, 1312-1320; PMID: 21346186.

Sankar, U., and Means, A.R. (2011). Gfer is a critical regulator of HSC proliferation. Cell Cycle 10(14), June 4, 2011, PMID: 21636978.

Wilkerson D.C., and Sankar, U. 2011. Mitochondria: A sulfhydryl oxidase and fission GTPase connect mitochondrial dynamics with pluripotency in embryonic stem cells. Int J Biochem Cell Biol Sep;43(9):1252-6; Epub 2011 May 13, PMID: 21605695

Recent Publications: Role of CaMKs in Other Cells and Cancer

Role of CaMKs in other cells and Cancer: The Sankar Lab team identified the mechanism by which CaMKIV links Toll-like receptor 4 signaling with the survival pathway in dendritic cells. Another collaborator manuscript showing the role of CaMKK1 in thymocyte aging is under review. More recently, this investigator team identified a novel cross-talk between CaMKIV and CaMKII in the regulation of proliferation of myeloid leukemia cells.

Monaco S., Rusciano MR, Maione AS., Soprano M., Gomathinayagam R., Todd LR., Campiglia P., Salzano S., Pastore L., Leggiero E., Wilkerson DC., Rocco M., Selleri C., Iaccarino G., Sankar U* and Illario M*. A novel cross-talk between calcium/calmodulin kinases II and IV regulates leukemia cell proliferation. Cell Signal. 2015 Feb;27(2):204-14. doi: 10.1016/j.cellsig.2014.11.007. Epub 2014 Nov 15. PMID: 25446257.

Faculty Research Team

23070-Sankar, Uma

Uma Sankar, PhD

Associate Professor of Anatomy, Cell Biology & Physiology

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Additional Research Team Members

Other research team members in the Sankar Lab include Ushashi Dadwal (postdoc), Elsa Mevel (postdoc), Mavis Irwin (postdoc), Justin Williams (IBMG PhD Student), Anuradha Valiya Kambrath (research analyst), Roshni Bharati Patel (MD student), Eric Chang (undergraduate student), and Matthew Hartman (undergraduate student).