Dr. Asok Mukhopadhyay

Educational Qualifications
M.Tech., Ph.D. (IIT, Delhi)

Postdoctoral Research
MD Anderson Cancer Centre, Houston, Texas

Research Interests
Hematopoiesis:
Expansion of hematopoietic stem cell, molecular and functional analysis of cells, self-renewal and differentiation of hematopoietic stem cells.

Regenerative medicine:
Adult stem cell plasticity, cell signaling in reprogramming hematopoietic cells into epithelial cells.

Cancer biology:
Identification of cancer stem cell (CSC) from ovarian cancer tissue, molecular signature of cancer stem cells, drug sensitivity of the CSC population.

SUMMARY OF CURRENT RESEARCH

Transplantation of hematopoietic stem cells (HSCs) cures many diseases of malignant and non-malignant in nature. It has been show that HSCs are multipotent that can differentiate into cell types of other germ layers. In spite of promising new applications, the success of HSC transplantation in different clinical applications has been found to depend on their availability. Providing sufficient number and acceptable quality of stem cells to patients at the right time are the challenges for stem cell biologists and technologists. Stem cell transplantation would be greatly facilitated by ex vivo expansion of a small number of cells from bone marrow (BM) or a cord blood sample. At present, no suitable system is available for ex vivo expansion of stem cells. It is also not clearly understood how HSCs are involved in the regeneration of damaged organs, other than bone marrow. The theme of research is to develop our knowledge-base on expansion of HSCs in culture and their applications as regenerative medicine.

Liver and kidney are most important organs, which undergo acute and chronic injuries due to toxic assault with chemicals and viral infection viruses. At present, whole organ transplantation is the only option available for treatment of patients at end stages. Shortage of donor organ, and their timely availability continues to be a worldwide problem. Our aim is to regenerate these damaged organs using stem cells for the patients' own body. We have identified a phenotype from mouse bone marrow (Lin^-OSMRb⁺) that transdifferentiate into albumin and CK-18 expressing hepatocytes in vitro. We have been involved in identifying bone marrow cells that are responsible for regeneration of damaged kidney tubular epithelial cells. Using GFP-chimeric mice it has been revealed that bone marrow cells are involved in regeneration of liver and kidney, which have undergone acute injury. By qPCR studies, we observed that differentiation of hematopoietic cells into hepatocytes is fusion independent. In vitro transdifferentiated hepatocytes were also found to engraft into healthy mouse liver. Presently, we are trying to understand molecular mechanisms for transdifferentiation of hematopoietic cells into hepatocytes and also in correcting hemophilia A in mouse model.

Hematopoietic stem cell is another area of our interest. We have been working for developing three-dimensional matrix based bioreactor for ex vivo culture of HSCs. Understanding molecular control for self-renewal and engraftibility of HSCs is the prime area of this study. Gene expression during the marrow regeneration phase, kinetics of HSC turnover in steady state and regenerating marrow are presently under investigation. We are also pursuing expansion of cord blood CD133⁺ cells, and phenotypic and functional analysis of the expanded cells.

PUBLICATIONS (last five years)

1. S. Khurana, A. Mukhopadhyay. In vitro transdifferentiation of adult hematopoietic stem cells: an alternate source of hepatocytes. J Hepatol, 2008 (press).

2. P.N.V. Gopal, S. Rentala, S. Roy, R. Wadhwa, S. Sharma, P.K. Roychaudhury, A. Mukhopadhyay, A.R. Ray. An artificial niche for expansion of long-term engraftable mouse hematopoietic cells. J Stem Cells, 2008 (press).

3. S. Khurana, A. Mukhopadhyay. Characterization of the potential sub- population of bone marrow cells involved in the repair of injured liver tissue. Stem Cells 25, 1439-1447, 2007.

4. M.M.S. Balla, S. Rentala, G. Reddy, S. Sharma, A. Mukhopadhyay. Fibronectin and laminin enhance engraftibility of cultured hematopoietic stem cells. Bichem. Biophy. Res. Commu. 350, 1000-1005, 2006.

5. S. Rentala, M.M.S. Balla, S. Khurana, A. Mukhopadhyay. MDR1 gene expression enhances long-term engraftibilityof cultured bone marrow cells. Bichem. Biophy. Res. Commu. 335, 957-964, 2005.

6. A. Mangla, A. Khare, V. Vineeth, N.N. Pandey, A. Mukhopadhyay, B. Ravindran, V. Bal, A. George, S. Rath. Pleiotropic consequences of Bruton Tyrosin kinase deficiency in myeloid lineages lead to poor inflammatory responses. Blood 104, 1191-1197, 2004.

7. T. Mashusudhan, S.S. Mazumder, A. Mukhopadhyay. Degeneration of   Stroma Reduces Retention of Homed Cells in Bone Marrow of Lethally Irradiated Mice. Stem Cell and Development 13, 173-182, 2004.

8. A. Mukhopadhyay, T. Madhusudhan, R. Kumar. Hematopoietic Stem Cells: Clinical Requirements and Developments in Ex-vivo  Culture. Adv. Biochem. Eng./Biotechnol. 86, 215-253, 2003.

9. G.M.K. Raju, S. Guha, A. Mukhopadhyay, L. Kumar, V.P. Kale, S. Mittal, D. Deka, S. Mohanty, V. Kochupillai. Colony-Stimulating Activity of Fetal Liver Cells:Synergistic Role of Stem Cell Factor in Bone Marrow Recovery from Aplastic Anemia. J hematother Stem Cell Res 12, 491-498, 2003.

10. T. Madhusudhan, A. Richhariya, S. Mazumder, A. Mukhopashyay. An in vitro model for grafting of hematopoietic stem cells predicts bone marrow reconstitution of myeloablative mice. J Hematother Stem Cell Res 12, 243-252, 2003.