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Faculty Profile

Chandan Guha, M.B.,B.S., Ph.D.

Dr. Chandan Guha

Professor, Department of Radiation Oncology

Professor, Department of Pathology

Vice Chair, Department of Radiation Oncology

 

Professional Interests

A)    Cell Transplantation to repair radiation injury. The radiation biology laboratory is investigating the molecular pathways of radiation-induced normal tissue injury. In a rodent model of radiation-induced liver damage, our group has demonstrated that intrasplenic or intraportal transplantation of hepatocytes can ameliorate the histopathological manifestations of hepatic radiation injury and significantly improve survival in rodents. We have extended this strategy and are examining whether intestinal stem cell growth factors, such as, R-spondin 1 and endothelial cell transplantation would ameliorate radiation-induced gastrointestinal tract injury.

B)    Preparative Irradiation to facilitate liver cell repopulation and stem cell engraftment in vivo. We were the first to use liver irradiation as a preparative regimen for liver cell transplantation. The long-term goal of this project is to develop liver cell transplantation as an alternative to orthotopic liver transplantation for patients with terminal liver diseases. We are examining whether a preparative regimen of focal irradiation, delivered by stereotactic radiosurgery (SRS), could ablate parenchymal cells in various organs and create a microenvironment that promotes the engraftment, growth and differentiation of progenitor / stem cell in vivo

C)    Immunomodulation of radiation therapy: Radiation-enhanced tumor vaccines. Irradiated tumors can potentially serve as a source of tumor antigens in vivo, where dying tumor cells would release various tumor antigens slowly over time. The long-term goal is to design novel tumor vaccines and amplify the immune response to such vaccines with primary tumor irradiation. Upon completion of these preclinical studies, we have designed a proof-of-principle clinical trial that will examine whether a combination of a pancreatic vaccine (PANVAC – vaccinia virus vectors expressing CEA and MUC1) and conventional 5-FU based chemo-radiation therapy would improve overall survival and induce strong tumor-specific immunity in patients with unresectable pancreatic cancer. We are also investigating whether High Frequency Ultrasound (HIFU) can augment the immune response to prostate cancer tumor vaccines.

D)    Development of novel radiosensitizers: ATM and polo-like kinase 1 as a target. Our long-term goal is to screen for drugs that can radiosensitize tumor cells without having undue normal tissue toxicity. Since, majority of tumor cells have aberrant G1 checkpoint, irradiated tumor cells depend upon the G2 checkpoint for survival. In order to increase the intrinsic radiosensitivity of tumor cells, novel drugs are being designed that target the cell cycle checkpoints, especially the G2 checkpoint.Molecular targets include proteins that participate in the DNA damage surveillance pathway, such as, ATM and Plk1.


 

Selected Publications

  1. Guha C, Sharma A, Gupta S, Alfieri A, Gorla GR, Gagandeep S, Sokhi R, Roy-Chowdhury N, Tanaka KE, Vikram B, and Roy-Chowdhury J. Amelioration of radiation-induced liver damage in partially hepatectomized rats by hepatocyte transplantation; Cancer Res (1999); 59: 5871-5874.
  2. Chakravarty PK, Alfieri A, Thomas EK, Beri V, Tanaka KE, Vikram B, and Guha C. Flt3-ligand administration after radiation therapy prolongs survival in a murine model of metastatic lung cancer; Cancer Res (1999); 59: 6028-6032.
  3. Guha C, Guha U, Tribius S, Alfieri A, Casper D, Chakravarty P, Mellado W, Pandita TK, and Vikram B. Antisense ATM gene therapy: a strategy to increase the radiosensitivity of human tumors; Gene Ther 2000; 7: 852-858.
  4. Guha C, Parashar B, Deb NJ, Sharma A, Gorla GR, Alfieri A, Roy-Chowdhury N, Roy-Chowdhury J, and Vikram B. Liver irradiation: a potential preparative regimen for hepatocyte transplantation; Int J Radiat Oncol Biol Phys (2001); 49: 451-457.
  5. Guha C, Parashar B, Deb NJ, Garg M, Gorla GR, Singh A, Roy-Chowdhury N, Vikram B, and Roy-Chowdhury J. Normal hepatocytes correct serum bilirubin after repopulation of Gunn rat liver subjected to irradiation/partial resection; Hepatology (2002); 36: 354-362.
  6. Takahashi M, Deb NJ, Kawashita Y, Lee SW, Furgueil J, Okuyama T, Roy-Chowdhury N, Vikram B, Roy-Chowdhury J, and Guha C. A novel strategy for in vivo expansion of transplanted hepatocytes using preparative hepatic irradiation and FasL-induced hepatocellular apoptosis; Gene Ther (2003; 10: 304-313.
  7. Menthena A, Deb N, Oertel M, Grozdanov PN, Sandhu J, Shah S, Guha C, Shafritz DA, and Dabeva MD. Bone marrow progenitors are not the source of expanding oval cells in injured liver; Stem Cells (2004); 22: 1049-1061.
  8. Guha C, Yamanouchi K, Jiang J, Wang X, Roy Chowdhury N, Santana A, Shapiro LJ, Salido E, and Roy-Chowdhury J. Feasibility of Hepatocyte Transplantation-Based Therapies for Primary Hyperoxalurias; Am J Nephrol (2005); 25: 161-170.
  9. Landis, C. S., Yamanouchi, K., Zhou, H., Mohan, S., Roy-Chowdhury, N., Shafritz, D. A., Koretsky, A., Roy-Chowdhury, J., Hetherington, H. P., and Guha, C. Noninvasive evaluation of liver repopulation by transplanted hepatocytes using 31P MRS imaging in mice. Hepatology, 44: 1250-1258, 2006.
  10. Mashalova, E. V., Guha, C., Roy-Chowdhury, N., Liu, L., Fox, I. J., Roy-Chowdhury, J., and Horwitz, M. S. Prevention of hepatocyte allograft rejection in rats by transferring adenoviral early region 3 genes into donor cells. Hepatology, 45: 755-766, 2007
  11. Basu, I., Cordovano, G., Das, I., Belbin, T. J., Guha, C., and Schramm, V. L. A transition state analogue of 5'-methylthioadenosine phosphorylase induces apoptosis in head and neck cancers. J Biol Chem, 282:21477-86, 2007.
  12. Mukhopadhaya, A., Mendecki, J., Dong, X., Liu, L., Kalnicki, S., Garg, M., Alfieri, A., Guha, C. Localized Hyperthermia Combined with Intratumoral Dendritic Cells Induces Systemic Antitumor Immunity. Cancer Res 67(16):1-9, 2007.

 

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Contact

Montefiore Medical Center
111 East 210th Street
Bronx, NY 10467

Tel: 718.920.2702
Fax: 718.231.5064
cguha@montefiore.org

 
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Media Coverage

NPR.com's Shots health blog interviews Dr. Chandan Guha about the radiation exposure and health risks faced by the workers who remain at the disabled Fukushima Daiichi nuclear power plant in Japan.

More media coverage