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Principal Investigator: Dr. Shilpee Dutt

Contact details

KS-314 Tata Memorial Centre,

ACTREC

Kharghar, Mumbai, India

Office Phone: (022)27405394

Laboratory Phone Extn: (022)27406216

 

Research Area

One Key Research Area: Therapy Resistance in cancer.

Special interests:Therapy Resistance, DNA Damage and Repair Pathways, Cancer Stem Cells, Epigenetics, Glioblastoma, Leukemia

About us: The broad focus of our laboratory is to gain insights into the radiation and chemo resistance-related molecular mechanisms in cancer. More specifically, our initial efforts are directed towards understanding the epigenetic regulation of chromatin structure and the DNA damage response (DDR). DNA damage and repair pathway is a well appreciated key player in conferring chemo and radiation resistance to the cancer cells. DNA lesions can trigger histone alterations, nucleosome repositioning and changes in higher-order folding of the chromatin fibre, all these changes in turn influence local DNA damage repair signalling around DNA damage and the mechanism of DNA repair, thus deciding the fate of the cell. However, how exactly epigenetics and chromatin structure are regulated and contribute in modulating DNA repair of the therapy resistant cancer cells is unclear. To understand these processes we employ biochemical, molecular biological, proteomic and genomic approaches and use radiation resistant (Glioblastoma) and chemotherapy resistant (Leukemia) in vitro cell line based model system developed in our laboratory. We collaborate with the clinicians at ACTREC and TMH to extend our findings from in vitro model system to patient samples and explore the possible translational benefits of our studies.

Projects

Projects: 

Project title: Understanding the role of chromatin and DNA damage repair pathway in Glioblastoma

PhD student: Ekjot Kaur

My research work primarily focuses on identifying the factors contributing to the survival and relapse of radiation treated Glioblastoma Multiforme tumor, which is a highly malignant brain cancer. The work involves understanding the role of DNA damage repair proteins in influencing the repair post radiation treatment and hence leading to survival. Since the repair capacity of a cell is modulated at the level of chromatin, my work also deals with identifying the differential epigenetic modifications contributing to the survival of radiation surviving cells as compared to the non-irradiated parent cells.

My journey in research began in 2006 with B. Sc in Biochemistry (Hons.) from the University of Delhi which was followed up with Master’s in Biotechnology from All India Institute of Medical Sciences (AIIMS, New Delhi) in the year of 2009. To pursue further into research, I joined Dr. Shilpee Dutt as a PhD student in 2011.

Project: Understanding therapy resistance in Glioblastoma using proteomics approach.

PhD Student: JACINTH RAJENDRA

Glioblastoma shows resistance to chemo and radiation therapy and often result in relapse. To understand the molecular mechanism behind the resistance we have modeled resistance in our lab using glioma cell lines and primary cultures from patient samples. For my Ph.D Iam analyzing the total proteome of parent, radiation escapers and the relapse cells from using quantitative proteomic approach i.e iTRAQ. Following which I’ll study the biological role of the identified proteins that promote radioresistance and also validate the proteins in the patient samples.

I have completed my B.Sc Biochemistry from University OF Delhi (2010) and M.Sc Biochemistry from University Of Calcutta (2012). I joined Dr.Shilpee Dutt’s lab in 2012 as a Ph.D student.

Project: Role of DNA damage repair pathways in chemoresistant leukemic cells

PhD Student: SAMEER SALUNKHE.

Resistance to chemotherapy is a major problem in the treatment of cancers and my research interest lies in understanding molecular mechanisms involved in establishment and maintenance chemoresistance. My PhD work primarily focuses on understanding the altered double strand break repair pathways in chemoresistant (Innate and acquired) leukemic cells.

I have completed my graduation and post-graduation studies in Biotechnology. I joined Dr. Shilpee Dutt Lab (ACTREC) in August 2012 as a PhD student. Cell and molecular biology are the subjects of my interest.

Project: Identification of Double Strand Break associated proteins in therapy sensitive and resistant cells.

PhD Student: RAHUL M. MOJIDRA

Double strand breaks are the most deleterious of all the DNA damage, if not repaired properly can lead to cell death or carcinogenesis. Double strand breaks is also the basis of chemotherapy and radiotherapy of cancer. Therefore understanding the mechanism of repair at the site of DSB is highly relevant. Iam trying to identify the proteins and histone modifications at site of the double strand breaks in a therapy sensitive and resistant leukemic cell. I will study DSBs generated by chemotherapeutic drugs like doxorubicin and mitoxantrone and also single site specific DNA double stand breaks using inducible I-Sce1 endonuclease system.

I have completed my Masters from Mumbai University with specialization in Biotechnology. I joined Dr. Shilpee Dutt as a Ph.D. JRF in 2013.

Project: Understanding the role of MCM and CDC6 in glioblastoma radiation resistance.

Project JRF- Sanket Shah

MCM proteins and CDC6 proteins are associated with DNA replication forks and cell cycle proteins respectively. Transcriptome data from radiation sensitive and resistant glioma cells shows high expression of these two proteins in radiation resistant cells. In my project I am trying to understanding how MCM proteins and CDC6 help glioma cells to confer radiation resistance.

Project: Role of histone methyl transferases in radiation resistance

Ankit Kushwaha

Histone methyltransferases (HMTs) are a class of enzymes that modify (transfer methyl group) histones at specific Lys or Arg residues. Reports of them being involved in carcinogenesis are rapidly accumulating. Our preliminary data shows upregulation of several HMTs in resistant glioma cells. Focus of my project is understand the molecular mechanisms by which these HMTs contribute to radiation resistance in glioblastoma.

Project: Identification of binding partners of gamma H2AX from HL60 and THP1 leukemic cell lines

Madhuri Puvvada

My Project involves identification of proteins associated with phosphorylated H2AX in Mitoxantrone sensitive and resistant leukemic cells. For this I do chromatin immuniprecipitation using antibody against endogenous gamma H2AX followed by identification of binding partners by mass spectrometer.

Ketaki Patkar : Scientific Assistant

Project: To understand the mechanism of chemo resistance in cancer we need to model resistance in laboratory. I am generating chemotherapeutic resistant sub cell lines from AML cells (HL60 and THP1). I will also generate resistant cells from other solid tumors to understand if the mechanisms of resistance are similar in all cancers or are cancer specific.

I have done my Masters degree in Biotechnology, B.Sc in Microbiology from Mumbai University. I joined Shilpee lab on 1st October 2011.

Members

Laboratory Members:

Present members:

1. Ekjot Kaur: (PhD-SRF)

2. Jacinth Rajendra (PhD-JRF)

3. Sameer Salunkhe (PhD-JRF)

4. Rahul Mojidra. (PhD-JRF)

5. Ketaki Patkar (Lab manager)

6. Ganesh Bejjanki (Lab technician)

7. Sanket Shah (Project-JRF)

8. Ankit Kushwaha (Trainee)

9. Madhuri Puvvada (Trainee)

Alumni

1.Sneha Berry(Trainee)

2.Sanobar (Trainee)

3.Vishwas (Trainee)

4.Gauri Patade (JRF)

5.Rachayata Dharmat (Trainee)

6.Priyadarshni Puri (JRF)

7.Akruti Shah (Trainee)

8.Priti Parikh (JRF)

9.Shailesh Jadhav (Trainee)

10.Alokananda Mukherjee(Trainee)

11.Joseph Fernandez( Trainee)

Publications

Select Publications:

1. Ghisolfi L*, Dutt S*, Ebert BL, Anderson P. Spontaneous stress granules in developing erythroid cells. BBRC 2012 Apr 20;420(4):768-74. (*equal contribution). Impact factor- 3.00

2. Narla A, Dutt S, McAuley JR, Al-Shahrour F, Hurst S, McConkey M, Donna Neuberg and Ebert BL. Dexamethasone and lenalidomide have distinct functional effects on erythropoiesis. Blood 2011 Apr 28. [Epub ahead of print] Impact factor- 10.5.

3. Dutt S, Cassoly E, Zimmermann- Dours M, Matasci M, Esther ST, Zimmermann DR. Versican V0 and V1 in the axon guidance during the developing peripheral nervous system. J Neuroscience 2011 Apr 6;31(14):5262-70.Impact factor- 8.2

4. Dutt S, Narla A, Lin K, Mullally A, Abayasekara N, Megerdichian C, Wilson FH, Currie T, Khanna-Gupta A, Berliner N, Kutok JL and Ebert BL. Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood 2011 Mar 3;117(9):2567-76. Epub 2010 Nov. Published as PLENARY ARTICLE. Impact factor- 10.5

5. Qingshen Y, Dutt S, Rong X, Graves K, Juszczynski P, Manis JP, Shipp MA. BBAP. Monoubiquitinates Histone H4 at Lysine 91 and Selectively Modulates the DNA Damage Response. Molecular Cell. 2009 Oct 9;36(1):110-20 Impact factor- 14.6

6. Jabara HH, Chaudhuri J, Dutt S, Dedeoglu F, Weng Y, Murphy MM, Franco S, Alt FW, Manis JP, Geha RS. B cell receptor crosslinking delays activation-induced cytidine deaminase induction and inhibits class switch recombination to IgE. J Allergy Clin Immunol. 2008 Jan;121(1):191-196. Impact factor- 9.7

7. Takeyama K, Monti S, Manis JP, Dal Cin P, Getz G, Beroukhim R, Dutt S, Aster JC, Alt FW, Golub TR, Shipp MA. Integrative analysis reveals 53BP1 copy loss and decreased expression in a subset of human diffuse large B-cell lymphomas. Oncogene. 2008 Jan 10;27(3):318-22 Impact factor- 7.1

8. Dutt S, Kleber M, Matasci M, Sommer L, Zimmermann DR. Versican V0 and V1 guide migratory neural crest cells. J Biol Chem. 2006 Apr 28;281(17):12123-313 Impact factor- 5.8

9. Dutt S, Matasci M, Sommer L, Zimmermann DR. Guidance of neural crest cell migration: the inhibitory function of the chondroitin sulfate proteoglycan, versican. ScientificWorld Journal. 2006 Sep 6;6:1114-7. Impact factor- 1.6

10. Basu U, Chaudhuri J, Alpert C, Dutt S, Ranganath S, Li G, Schrum JP, Manis JP, Alt FW. The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation. Nature. 2005 Nov 24; 438(7067): 508-11 Impact factor- 34.4

Links: Applications / online sources developed by the Department

Awards / Honors:

1. 2014 Shri Sitaram Joglekar award to Ph.D student Ms Ekjot for the best oral presentation at 33rd Annual Convention of Indian Association for Cancer Research (IACR) 13-15 February.

2. 2012 Awarded poster prize to Ms. Priyadarshini Puri. Three posters presented by students at 2nd Global Cancer Genomics Consortium (GCGC) TMC symposium 19-20 November 2012 at ACTREC.

3. 2011 Manuscript published as plenary article in March edition of journal ‘Blood’

4. 2009 Oral presentation at American Society of Hematology meeting, 2009, New Orleans, USA

5. 2005 Awarded Swiss National Science Foundation Postdoctoral fellowship from the Govt. of Switzerland, as an outstanding promising candidate to pursue postdoctoral research in USA.

6. 2005 Certificate of successfully completing 4 years of the international Ph.D program in Neuroscience from Neuroscience center Zurich (ZNZ).

7. 2004 Awarded a prize for best oral presentation, University of Zurich.

8. 2003 Awarded complete travel grant from Neuroscience Centre Zurich (ZNZ).

9. 2002 Best oral presentation award, The Connective Tissue Society meeting, Ulm, Germany

10.1998 Awarded the Junior Research Fellowship by the University Grants Commission, Ministry of Human Resource& Development, and Government of India.

11. 1998 Qualified Graduate Aptitude Test in Engineering (GATE), Conducted by Department of Education, Ministry of Human Resource Development, Government of India.

12. 1998 Qualified NET (National Eligibility Test) for CSIR-UGC JRFship and Eligibility for Lectureship

13. 1994 First Position in B.Sc in College, University of Delhi.

14. 1995 Selected as best cadet to represent college at Republic Day parade.

Affiliations: Homi Bhabha National Institute (HBNI)

Member:

Society of Neuroscience

American Society of Hematology

Indian Association of Cancer Research

Contact Us

Advanced Centre for Treatment, Research and Education in Cancer

Kharghar, Navi Mumbai - 410 210, india

Phone:+91-22-2740 5000

Fax: +91-22-2740 5085

E-mail : This email address is being protected from spambots. You need JavaScript enabled to view it.