Dr. Sheo Mohan Singh
Director, ICSCCB, New Delhi, India

MSc Biotechnology, University of Kent at Canterbury, UK
PhD Summa cum laude, Human Biology, LMU University of Munich, Germany

Postdoctoral Fellowships:
1. University of Massachusetts Medical School, Worcester, MA, USA
2. Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
3. Mount Sinai School of Medicine, New York, NY, USA

Dr. Singh has done his MSc from the University of Kent at Canterbury, UK and PhD from the LMU University of Munich, Germany. He went on to do his postdoctoral training at the University of Massachusetts Medical School, USA, Leeds Institute of Molecular Medicine, UK, and Mount Sinai School of Medicine, USA. His current research interests are described below.

Role of transcription factors and leukemic fusion proteins in hematopoiesis, stem cells and pathogenesis of leukemias:
The rational design of targeted therapies for cancer requires the discovery of the precise role of transcription factors and signaling pathways in cancer cells, and the determination of their biological functions. Based on these discoveries a small molecule drug against a specific type of cancer could be developed and tested. One example of this approach being successfully used in treatment of chronic myeloid leukemia (CML) patients is STI-571 (marketed as Gleevec) which was developed against leukemic fusion protein BCR-ABL. Acute myeloid leukemia (AML) is a disease that is characterized by an abnormal accumulation of granulocytic or monocytic precursor cells in the bone marrow and blood as a result of chromosomal translocations or aberrant mutations in signaling pathways.

These abnormalities promote aberrant proliferation, block differentiation and/or prevent cell death leading eventually to the development of leukemia. For example, AML1-ETO is a leukemic fusion protein which is found in approximately 12-15% of AML patients and in approximately 40-50% of AML patients with M2-subtype. In recent years it has been shown that transcription factors are important and sometimes absolutely required for the differentiation of blood cells from the bone marrow stem cells. It’s also reported that the disruption of this normal function of transcription factors by leukemic fusion proteins or by disrupted signaling pathways might play a role in the development of leukemia disease. In view of the important role of transcription factors and leukemic fusion proteins in the pathogenesis of leukemia, my current interests are the following:

1. Proteomic systems biology of t(8;21)-AML: How leukemic fusion protein AML1-ETO and myeloid transcription factors C/EBPs (CCAAT enhancer binding proteins) regulate differentiation inhibitory factor NM23?
2.  How AML1-ETO and BCR-ABL (another leukemic fusion protein) regulate polycomb group protein Bmi1 and whether Bmi1 is required for the leukemic transformation of stem cells by these fusion proteins?
3. Can myeloid transcription factors induce differentiation of embryonic stem cells and how leukemic fusion proteins AML1-ETO or BCR-ABL may affect this process?
4. Development of RNAi technology for targeted disruption of leukemic fusion genes.

1. Singh,S.M.*, Behre,G.*, Liu,H., Bortolin,L.T., Christopeit,M., Radomska,H.S., Rangatia,J., Hiddemann,W., Friedman,A.D., Tenen,D.G. (2002). Ras signaling enhances the activity of C/EBPalpha to induce granulocytic differentiation by phosphorylation of serine 248. Journal of Biological Chemistry 277:26293-26299, *Authors contributed equally.

2. Behre,G., Reddy,V.A., Tenen,D.G., Hiddemann,W., Peer Zada, A.A., Singh,S.M. (2002). Proteomic analysis of transcription factor interactions in myeloid stem cell development and leukemia. Expert Opinion on Therapeutic Targets 6:491-495.

3. Vangala,R.K., Neumann,M.S., Rangatia,J., Singh,S.M., Tenen,D.G., Hiddemann,W., Behre,G. (2003). The myeloid master regulator PU.1 is inactivated by AML1-ETO in t(8;21) myeloid leukemia. Blood 101:270-277.

4. Rangatia,J., Vangala,R.K., Singh,S.M., Peer Zada,A.A., Elsässer,A., Kohlmann,A., Haferlach,T., Tenen,D.G., Hiddemann,W., Behre,G. (2003). Elevated c-Jun expression in acute myeloid leukemias inhibits C/EBPalpha DNA binding via leucine zipper domain interaction. Oncogene 22(30):4760-4764.

5. Zada,A.A., Singh,S.M., Reddy,V.A., Meisel,A., Elsässer,A., Haferlach,T., Tenen,D.G., Hiddemann,W., Behre,G. (2003). CD44 ligation inhibits proliferation in acute myeloid leukemia cells by downregulating c-Jun expression and blocking cell cycle. Oncogene 22(15):2296-2308.

6. Trivedi,A.K., Bararia,D., Christopeit,M., Peerzada,A.A., Singh,S.M., Kieser,A., Hiddemann,W., Behre,H.M., Behre,G. (2007). Proteomic identification of C/EBP-DBD multiprotein complex: JNK1 activates stem cell regulator C/EBPalpha by inhibiting its ubiquitination. Oncogene 26(12):1789-1801.

7. Singh,S.M., Trivedi,A.K., Behre,G. (2008). C/EBPalpha S248A mutation reduces granulocytic differentiation in human leukemic K562 cells. Biochem Biophys Res Commun.:369(2):692-4.

8. Trivedi,A.K., Pal, P., Behre,G., Singh,S.M. (2008). Multiple ways of C/EBPalpha inhibition in myeloid leukemia. European Journal of Cancer: 44(11):1516-23.

9. Singh, S.M., Trivedi, A.K., Lochab, S., Christopeit, M., Hiddemann, W., Behre, G. (2010).  Proteomics of AML1/ETO Target Proteins: AML1–ETO Targets a C/EBP–NM23 Pathway. Clinical Proteomics: 6(3):83-91.

10. Singh, S.M. (2010).  Biotechnology, Stem Cells and Molecular Medicine: Future Perspective. Deccan Chronicle, February 2010.

11. Kanaujiya, J.K., Lochab, S., Pal, P., Christopeit, M., Singh, S.M., Sanyal, S., Behre, G., Trivedi, A.K. (2011).  Proteomic approaches in myeloid leukemia. Electrophoresis 32: 357-67.