Research Department:
After completing my Master’s in Biotechnology from Osmania University, I moved to USA for my graduate work where I received my Ph.D. from Utah State University under the guidance of Prof DaryllDeWald.Later, I did my postdoctoral research in the laboratory of Prof. Danny Welch at The University of Kansas Medical Center.This was followed by a stint as a research fellow at the Institute of Molecular and Cell Biology (IMCB)inSingapore. In July2016, I joinedSRM University, Department of Genetic Engineering as an Assistant Professor.
My approach to science has involved using creative basic techniques to answer challenging questions related to human health.The focus of my research career has centred on studying the biology of cancer metastasis, specifically metastasis suppressor genes. In my doctoral studies, I Showed the metastasis suppressor gene BRMS1specifically reduced the expression of oncogenic receptors in highly metastatic cells leading to them remaining dormant at secondary sites. As a postdoctoral fellow, I studied another metastasis suppressor gene KISS1. A highlight of my work was the identification of critical post-translational modifications (PTMs) in KISS1. As an independent investigator, I will utilise my cellular and molecular expertise to continue gaining mechanistic insights on metastasis suppressor genes.
The concept that successful metastasis requires tumourcells to overcome multiple inherent boundaries, both at tissueand molecular levels, forms the basis of my research.Indeed,the ability of a metastatic cancer cell to penetratenonpermissive boundaries is a hallmark of metastasis. However, we still donot know the signalling mechanisms/molecules that drive and/or impede this process. One such class of molecules that has gained tremendous traction over the years are the metastasis suppressor genes. They inhibit metastasis without interrupting primary tumour growth. How metastasis suppressor genes work is largely unknown. Therefore, an understanding of their mechanism of action will help develop a more realistic and less aggressive approach to control cancer cell proliferation instead of relying on therapies that cause drug resistance resulting in more aggressive treatment strategies and concomitant deleterious side effects.
Metastatic cascade and metastasis suppressor’s mechanism of actionMetastasis suppressors arelisted under each step in the metastatic cascade at which they have been experimentally shown to suppress. (Journal of Molecular Medicine, 2014)
The main goal of my laboratory is to understand how metastasis suppressor genes work. To accomplish this broad objective our focus has centred on studying the mechanism of action of two metastasis suppressor genes BRMS1 and KISS1. Furthermore, we have also ventured into studying ultrastructural and biomechanical properties of cancer cells.The research in our laboratory spans from genes toin vivo studies with expertise in molecular biology, imaging, biochemistry, cell culture and animals to address our questions.
M.Tech
- Aishwarya P.G
Selected Publications
- DeWald DB, Ozaki S, Malaviya S, Shope JC, Manabe K, Crosby L, Neilsen P, Johnston D, Harihar S, and Prestwich GD. Cellular calcium mobilization in response to phosphoinositide delivery. Cell Calcium (2005) 38, 59-72
- Zhang L, Huang W, Tanimura A, Morita T, Harihar S, DeWald DB, and Prestwich GD. Synthesis and Biological Activity of Metabolically Stabilized Cyclopentyl Trisphosphate Analogues of D-myo-Ins(1,4,5)P(3). ChemMedChem (2007) 10:1281-1289
- Vaidya KS, Harihar S, Phadke PA, Stafford LJ, Hurst DR, Hicks DG, Casey G, DeWald DB, Welch DR. Breast cancer metastasis suppressor-1 differentially modulates growth factor signaling. J BiolChem (2008) Oct 17; 283(42):28354-60
- Wu Y, McEwen GD, Harihar S, Baker SM, DeWald DB, Zhou A. BRMS1 expression alters the ultrastructural, biomechanical and biochemical properties of MDA-MB-435 human breast carcinoma cells: an AFM and Raman Microspectroscopy Study. Cancer letters(2010) Jul 1;293(1):82-91
- Bohl CR*,Harihar S* Denning WL*, Sharma R and Welch DR. Metastasis suppressors in breast Cancers: mechanistic insights and clinical potential J. Mol Med (2014) Jan;92(1):13-30* equal contribution
- Harihar S, Pounds KM, Iwakuma T, Seidah NG and Welch DR. Furinis the major proprotein convertase required for KISS1-to-kisspeptin processing PLoS One. (2014) Jan 13;9(1)
- Xiao L, Harihar S, Welch DR and Zhou A. Imaging of epidermal growth factor receptor on single breast cancer cells using surface-enhanced Raman spectroscopy Anal ChimActa (2014) Sep 16;843:73-82
- Rangarajan P, Subramaniam D, Paul S, Kwatra D, Palaniyandi K, Islam S, Harihar S,Ramalingam S, Gutheil W, Putty S, Pradhan R, Padhye S, Welch DR, Anant S, Dhar A. Crocetinic acid inhibits hedgehog signaling to inhibit pancreatic cancer stem cells Oncotarget (2015) Sep 29;6(29):27661-73
- Li Q, Xiao L, Harihar S, Welch DR, Vargis E and Zhou A. In vitro biophysical, microspectroscopic and cytotoxic evaluation of metastatic and non-metastatic cancer cells in responses to anti-cancer drug Analytical methods (2015) Dec, 7(24): 10162-69
- Kurahara H, Bohl CR, Natsugoe S, Nishizono Y, Harihar S, Sharma R, Iwakuma T and Welch DR. Suppression of Pancreatic Cancer Growth and Metastasis by HMP19 Identified through In Vivo Genom-Wide shRNA Screening Intl Journal of Cancer (2016) Aug 1; 139(3): 628-38
- Li Q, Tian X, Harihar S, Li Q, Li L, Welch DR and Zhou A. Gd2O3-doped silica @ Au Nanoparticles for In Vitro Imaging Cancer Biomarkers Using Surface-Enhanced Raman scattering (Under revision Journal of Biomedical Optics)
Conference Abstracts
- DeWald DB, Harihar S and Welch DR. Breast Cancer Metastasis Suppressor 1 Reduces Epidermal Growth Factor Signaling in MDA-MB-435 Cells.American Association for Cancer Research, Washington D.C, (2006).
- Vaidya KS, Harihar S, Phadke P, Hicks D, Casey G, DeWald DB and Welch DR Differential Signaling Imposed by BRMS1 as a Potential Mechanism for Differential Growth of Breast Cancer Cells. American Association for Cancer Research, Los Angeles (2007)
- Vaidya KS, Harihar S, Phadke P, Stafford L, DeWald DB and Welch DR Breast Cancer Metastasis Suppressor 1 (BRMS1) Selectively Modulates Growth Factor Signaling. American Association for Cancer Research, San Diego (2008)
- Harihar S,La J, Xie Y,Welch DR and DeWald DB. Breast Cancer Metastasis Suppressor 1 reduces Phosphoinositide Signaling and Invasive Potential of MDA-MB-435 cells. Joint Metastasis Research Society - AACR Conference on Metastasis, Vancouver BC, Canada (2008)
- Vaidya KS, Harihar S, Phadke P, Stafford L, Hurst D, DeWald DB and Welch DR Breast Cancer Metastasis Suppressor 1 Selectively Modulates Growth Factor Signaling at Multiple Steps of the PI3K-Akt CascadeJoint Metastasis Research Society - AACR Conference on Metastasis, Vancouver BC, Canada (2008)
- Harihar S, La J,Welch DR and DeWald DB. Differential Regulation of Type I Phosphatidylinositol 4-Phosphate 5-kinase isoforms in MDA-MB-435 cells by BRMS1. American Association for Cancer Research, Denver, CO, (2009)
- Harihar S, Pounds KM,Iwakuma T, Seidah NG and Welch DR. Furinis required for processing KISS1 to Kisspeptins. American Association for Cancer Research, Washington DC (2013)
- Harihar S, Hampton KR,Iwakuma T, Seidah NG and Welch DR. Furin mediated processing and phosphorylation are critical post-translational modifications in KISS1. American Association for Cancer Research, San Diego CA (2014)
- Bohl CR, Kurahara H, Natsugoe S, Nishizono Y, Harihar S, Iwakuma T and Welch DR Identification and biochemical characterization of HMP19, a tumor/metastasis suppressor in pancreatic cancer. American Association for Cancer Research, San Diego CA (2014)
- Cell Signaling-Animal
- Enzyme Engineering
- Stem Cell Biology and Gene Therapy
- Ethics IPR
- Molecular Techniques Laboratory
- Gene Expression Laboratory
Contact:
Dr.SitaramHarihar
Assistant Professor
Department of Genetic Engineering
SRM University, Kattankulathur- 603203
Kanchipuram District, Tamil Nadu, INDIA
Email:sitaramharihar.r@ktr.srmuniv.ac.in