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Samisubbu R. Naidu, Ph.D.

Assistant Research Professor

Although I began my independent research program to understand cell death mechanisms in melanoma, our investigations led us to the understanding that metabolic plasticity enable melanoma to resist cell death mechanisms. We are focusing on the following projects with a long-term goal of developing an effective therapy for melanoma.

1. Define the mechanism of ferroxitosis: We reported a novel iron and oxygen dependent cell death called ferroxitosis. Redox cycling agent menadione promotes ferroxitosis in cells cultured under normoxic condition, yet activation of ferroxitosis under hypoxia is contingent upon depletion or inhibition of glycolytic enzyme PKM2. We are investigating the role of nuclear and/or cytosolic functions of PKM2 as well as mitochondrial Complexes in activation of ferroxitosis.
2. Dissect the mechanism of acetate metabolism in melanoma: We reported that acetate metabolism synergizes with glutamine to support melanoma cell survival and tumor growth in a glucose-independent manner. BRAF mutant melanomas rapidly adapt to acetate metabolism in the absence of glucose. Because resistance to BRAF inhibitor therapy involves gain of mitochondrial metabolism, we are currently investigating the mechanism of mitochondrial acetate metabolism.
3. Define the metabolic check points in hematopoietic stem cells: We are closely working with Dr. Broxmeyer to define the metabolic determinants that control hematopoietic stem cell self-renewal and expansion. My goal is to utilize the knowledge gained in melanoma metabolism to promote expansion of hematopoietic stem cell.

  • Lakhter AJ, Kanginakudru S, Warren S, Touloukian CE, Boissy RE, Naidu SR, (2013) Impaired PIASy-Tip60 signaling weakens activation of p53 in melanoma. Melanoma Research (3) 213-217.
  • Lakhter AJ, Sahu RP, Sun Y, Kaufmann WK, Androphy EJ, Travers JB, Naidu SR, (2013) Chloroquine Promotes Apoptosis in Melanoma Cells by Inhibiting BH3 domain Mediated PUMA Degradation. The Journal of investigative dermatology, 2013. 133(9): p. 2247-54. Commentary: The Journal of investigative dermatology, 2013. 133(9): p. 2133-5.
  • Lakhter AJ, Hamilton J, Dagher PC, Hato T, Dong CX, Mayo LD, Harris RA, Shekhar A, Ivan M, Brustovetsky N, Naidu SR, (2014) Ferroxitosis: A form of cell death from inhibition of both oxidative phosphorylation and HIF-1a/PKM2-dependent glycolysis. Oncotarget, 5(24) 12694-12703.
  • Lakhter AJ, Lahm T, Broxmeyer HE, Naidu SR, (2016) Golgi associated HIF1a serves as a reserve in melanoma cells. Journal of Cellular Biochemistry; 117(4):853-9. 
  • Lakhter AJ, Hamilton J, Konger RL, Brustovetsky N, Broxmeyer HE, Naidu SR, (2016) Glucose-independent acetate metabolism promotes melanoma cell survival and tumor growth. Journal of Biological Chemistry 291(42):21869-879. 
  • Ph.D., 2000: University of Pune and Washington State University
  • Postdoctoral, 2000-2001: University of Texas
  • Postdoctoral, 2001-2010: University of Massachusetts Medical School
  • Assistant Professor, 2010-2015: Indiana University School of Medicine, Department of Dermatology.

Department of Microbiology and Immunology | IU School of Medicine | 635 Barnhill Drive, MS 420 | Indianapolis, IN 46202 | (317) 274-0506