Sudarshan Anand, PhD
Noncoding RNAs and Tumor microenvironment
2007 Johns Hopkins University School of Medicine, Baltimore, MD
2001 Birla Institute of Technology and Science, Pilani, India
M.Sc (with Honors) Biological Sciences and B. Pharm (with Honors); Dual-degree program
2013-2014 Assistant Research Scientist, Moores UCSD Cancer Center, University of California, San Diego
2007-2013 Postdoctoral Scholar, Moores UCSD Cancer Center, University of California, San Diego
Fellowships, Awards and Honors:
2013 Invited speaker, Moores Cancer Center Noon Scientific Lecture, UCSD, CA
2013 Invited speaker, Knight Cancer Institute, OHSU, Portland, OR
2013 Invited speaker, Yale Cancer Center, New Haven, CT
2012 Invited speaker, NIH K Award Cardiovascular Investigator's Meeting, Bethesda, MD
2012 NIH/NHLBI K99/R00 Pathway to Independence Award
2012 Invited speaker, Smooth Muscle FASEB Summer Research Conference, Snowmass, CO
2012 Invited speaker, Topics and Advances in Internal Medicine, San Diego, CA
2011 Invited speaker, ‘Building Better Blood Vessels’, ASN Annual meeting, Philadelphia, PA
2009 American Heart Association Postdoctoral Fellowship
2004 FOCIS travel award, International Immunology meeting, Montreal, CA
1999 Summer Research Fellowship, JNCASR, Bangalore, India
1994 Gifted Youth Program for exceptional high school students, Anna University, India
Summary of Current Research Interests:
The host microenvironment that supports the growth of tumors encounters a variety of insults during tumor progression. Particularly with the increasing use of genotoxic agents in cancer, there is a significant induction of DNA damage in both tumor cells and the microenvironment. While the DNA damage, cell cycle and apoptosis pathways have been elucidated in the context of tumor cells and their aberrant genomes, it is unclear how genetically normal host cells in the microenvironment perceive and respond to DNA damage. Understanding what factor(s) mediate DNA damage responses in the host cells will a) provide potential targets for sensitizing the tumor microenvironment to genotoxic stress and b) contribute fundamental mechanistic insights into how the different host cell types in the microenvironment handle insults and injuries.
My research interests are focused on understanding how non-coding RNAs shape the tumor microenvironment particularly in the context of various stressors such as genotoxic, inflammatory and oxidative stress. Specific long-term goals of the laboratory include:
1) Understanding the microRNA-target networks in the tumor vasculature and how they handle genotoxic stress such as radiation and chemotherapy.
2) Characterizing the influence of non-coding RNAs on immune co-stimulation in the tumor microenvironment.
3) Engineering host cells with microRNA-coded logic gates to enable tumor infiltration, surveillance and microenvironment reprogramming capabilities. Our laboratory will use a number of approaches ranging from RNA profiling to functional genomics and in vivo screens to identify relevant non-coding RNAs. We will also utilize a number of cellular assays, 3D co-culture systems and mouse models of cancers to understand the biological function of these RNAs. These complementary approaches will provide a framework to address how small perturbations across critical nodes of a network have significant pathological consequences in the tumor microenvironment.
K99/R00 Pathway to Independence Award (NIH/NHLBI). 06/01/2012-02/28/2017 Title: MicroRNA regulation of cell survival in angiogenesis and vessel maturation
1. Westenskow, P.D., Kurihara, T., Aguilar, E., Scheppke, E.L., Moreno, S.K., Marchetti, V., Michael,I.P., Anand, S., Nagy, A., Cheresh, D.A., and Friedlander, M. Inhibiting the Ras pathway prevents neovascularization by repressing endothelial cell sprouting. Journal of Clinical Investigation. 2013. 123(11):4900–4908
2. Lau SKM, Shields DJ, Murphy EA, Desgrosellier JS, Anand S, Huang M, Kato S, Lim S-T., Weis SM, Stupack DG, Schlaepfer DD and Cheresh DA.: EGFR-Mediated Carcinoma Cell Metastasis Mediated by Integrin αvβ5 Depends on Activation of c-Src and Cleavage of MUC1. PLoS ONE 2012. 7:e36753.
3. Sakoda Y*, Anand S*, Zhao Y*, Park J-J, Liu Y, Kuramasu A, van Rooijen N, Strome SE, Hancock WW, Chen L, and Tamada K. Regulation of Hypoxia-Inducible Factor-1α and Erythropoiesis by Herpesvirus Entry Mediator. Journal of Clinical Investigation. 2011. 121(12): 4810-9, * Equal Contribution.
4. Huang M, Anand S, Murphy EA, Desgrosellier JS, Stupack DG, Shattil SJ, Schlaepfer DD, Cheresh DA. EGFR-dependent pancreatic carcinoma cell metastasis via Rap1 activation. Oncogene. 2011. Advance Online Publication.
5. Park J-J*, Anand S*, Zhao Y*, Matsumura Y, Sakoda Y, Kuramasu A, Strome SE, Chen L, Tamada K. Expression of anti-HVEM single chain antibody on tumor cells induces tumor-specific immunity with long-term memory. Cancer Immunology & Immunotherapy. 2012. 61(2): 203-14. * Equal contribution.
6. Mielgo A, Seguin L, Huang M, Camargo MF, Anand S, Franovic A, Weis SM, Advani SJ, Murphy EA, Cheresh DA: A MEK-independent role for CRAF in mitosis and tumor progression. Nature Medicine 2011. 17(12): 1641-5.
7. Anand S, Majeti BK, Acevedo LM, Murphy EA, Mukthavaram R, Scheppke L, Huang M, Shields DJ, Lindquist JN, Lapinski PE, et al.: MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nature Medicine 2010, 16:909-914.
8. Murphy EA, Shields DJ, Stoletov K, Dneprovskaia E, McElroy M, Greenberg JI, Lindquist J, Acevedo LM, Anand S, Majeti BK, et al.: Disruption of angiogenesis and tumor growth with an orally active drug that stabilizes the inactive state of PDGFRbeta/B-RAF. Proceedings of the National Academy of Sciences of U S A 2010, 107:4299-4304.
9. Park JJ, Omiya R, Matsumura Y, Sakoda Y, Kuramasu A, Augustine MM, Yao S, Tsushima F, Narazaki H, Anand S, et al.: B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T cell tolerance. Blood 2010, 116(8):1291-1298.
10. Zhu G, Augustine MM, Azuma T, Luo L, Yao S, Anand S, Rietz AC, Huang J, Xu H, Flies AS, et al.: B7-H4-deficient mice display augmented neutrophil-mediated innate immunity. Blood 2009, 113:1759-1767
11. Xu Y, Flies AS, Flies DB, Zhu G, Anand S, Flies SJ, Xu H, Anders RA, Hancock WW, Chen L, et al.: Selective targeting of the LIGHT-HVEM costimulatory system for the treatment of graft-versus-host disease. Blood 2007, 109:4097-4104.
12. Anand S, Wang P, Yoshimura K, Choi IH, Hilliard A, Chen YH, Wang CR, Schulick R, Flies AS, Flies DB, et al.: Essential role of TNF family molecule LIGHT as a cytokine in the pathogenesis of hepatitis. Journal of Clinical Investigation 2006, 116:1045-1051.
1. Anand S.: A brief primer on microRNAs and their roles in angiogenesis. Vascular Cell 2013, 5:2. In press.
2. Anand S, Cheresh DA.: Emerging role of microRNAs in the regulation of angiogenesis. Genes & Cancer 2011, 2:1134-1138.
3. Anand S, Cheresh DA.: MicroRNA-mediated regulation of the angiogenic switch. Current Opinion in Hematology 2011, 18:171-176.
4. Anand S, Chen L: Control of autoimmune diseases by the B7-CD28 family molecules. Current Pharmaceutical Design 2004, 10:121-128.
Selected Poster Presentations:
1. Anand S, Advani SJ, Scheppke, L, Cheresh DA. MicroRNA-34 functions as an endothelial ‘apoptomir’ by regulating NOTCH signaling. 6th Annual Frontiers of Clinical Investigation Symposium - Vascular Biology 2011: Bench to Bedside. La Jolla, CA
2. Anand S, Majeti BK, Acevedo LM, Murphy EA, Mukthavaram R, Scheppke L, Huang M, Shields DJ, Lindquist JN, Weis SM, Cheresh DA. MicroRNA-132 functions as a novel angiogenic switch by targeting p120RasGAP. Angiogenesis 2010, Hyatt Regency, La Jolla, CA
3. Anand S, Majeti BK, Acevedo LM, Murphy EA, Mukthavaram R, Scheppke L, Huang M, Shields DJ, Lindquist JN, Weis SM, Cheresh DA. MicroRNA-132 functions as a novel angiogenic switch by targeting p120RasGAP. American Society for Cell Biology Annual Meeting 2009, San Diego, CA
4. Anand S, Majeti BK, Acevedo LM, Murphy EA, Mukthavaram R, Scheppke L, Huang M, Shields DJ, Lindquist JN, Weis SM, Cheresh DA. MicroRNA-132 functions as a novel angiogenic switch by targeting p120RasGAP. Gordon Research Conference-Angiogenesis 2009, Newport, RI
5. Anand S, Tamada K., Wang P, Hilliard A, Lau, J.S., Flies DB, Wang CR, Schulick R, Zhu G, Chen YH, Chen L. LIGHT, a cell surface TNF superfamily ligand, induces acute liver injury after enzymatic cleavage in vivo. 12th International Congress of Immunology, 2004, Montreal, CA. * Selected for oral presentation
Professional Society Memberships:
2008-present Associate member, American Association for Cancer Research
2011-present Member, American Association for the Advancement of Science
US Patent Applications:Anand, S., Advani S.J., Cheresh, D.A. # 61/547,934- Use of microRNAs and microRNA inhibitors to modulate blood vessel growth, patterning, tumor growth and malignant disease.
Anand, S., Seguin L., Cheresh, D.A. # 61/843,417- Compositions and methods for treating cancer and diseases and conditions responsive to cell growth inhibition.
- Emerging Role of Micro-RNAs in the Regulation of Angiogenesis.
- A brief primer on microRNAs and their roles in angiogenesis.
- A MEK-independent role for CRAF in mitosis and tumor progression.
- Disruption of angiogenesis and tumor growth with an orally active drug that stabilizes the inactive state of PDGFRbeta/B-RAF.
- EGFR-dependent pancreatic carcinoma cell metastasis through Rap1 activation.
- EGFR-mediated carcinoma cell metastasis mediated by integrin αvβ5 depends on activation of c-Src and cleavage of MUC1.
- MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis.
- MicroRNA-mediated regulation of the angiogenic switch.
- Ras pathway inhibition prevents neovascularization by repressing endothelial cell sprouting.
- Herpesvirus entry mediator regulates hypoxia-inducible factor-1α and erythropoiesis in mice.