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Raghbir Athwal, PhD

Raghbir Athwal, PhD

 

Professor, Fels Institute for Cancer Research

and Molecular Biology

Professor of Pathology and Laboratory Medicine

Telephone:  215-707-6931

Fax:  215-707-2989

Email: raghbir.athwal@temple.edu

 

Department of Pathology and Laboratory Medicine

Fels Institute for Cancer Research and Molecular Biology

 

Educational Background:

 

Punjab Agricultural University

Punjab, India

BSc Biology, 1960-1964

MSc Genetic, 1964-1966

 

University of Missouri

Columbia, MO

PhD Genetics, 1967-1971

 

University of Missouri

Division of Human Genetics, Department of Pediatrics

Postdoctoral Fellow, 1971-1973

 

Howard University Medical School

Washington, DC

Laboratory of Biochemistry

Postdoctoral Fellow, 1973-1975

 

National Cancer Institute

National Institutes of Health

Bethesda, MD

Research Associate, 1975-1978

 

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Research Interests:

 

The long term goal of our research is to elucidate molecular and genetic pathways involved in the regulation of normal cell growth leading to senescence, and their role in the development of cancer and cellular aging. Normal mammalian cells, unlike cancer cells, multiply only for a finite number of generations, and eventually enter a state of irreversible growth arrest, “the replicative senescence”. Applying a functional strategy, we have identified four cell senescence genes, three on chromosome 6q and one on 16q. The ectopic expression of one of the genes (SEN6A), cloned in a retroviral vector, induce senescence in ovarian and breast tumor cells, and lead to premature senescence in normal human fibroblasts. SEN6A is either rearranged or not expressed in many of the breast and ovarian tumor cells, suggesting that it plays a role in the etiology of breast and ovarian cancers. Further pursuit of our research includes delineation of mechanisms of SEN6A inactivation in tumor cells; and identifies signaling pathways involved in the functioning of SEN6A. Our preliminary observations revealed that SEN6A may be involved in DNA damage-repair response through a pathway related to the production of Reactive Oxygen Species (ROS). These finding evoked our interest to study genes associated with DNA damage – repair pathways in relation to cellular senescence. Signaling pathways that regulate cell senescence has gained significance as emerging targets for cancer therapy.

 

 

 Ectopic expression of cloned SEN6A gene  induce senescence in human cells

 Ectopic expression of cloned SEN6A gene  induce senescence in human cells: A. Expression of EGFP tagged SEN6A in human cells; B.; Phase contrast photomicrograph of same cells and C. β-gal stained SEN6A  expressing senescent cells.

In another project, we are investigating the molecular mechanisms of virus induced malignant transformation of human cells. These studies are driven by the hypothesis that immortalization of human cells requires the disruption of specific genes through viral integration. Using SV40 mediated immortalization of human fibroblasts as a model system; we have isolated a human DNA segment, corresponding to the viral insertion site. The introduction of this cloned human DNA segment, into SV40 immortalized cells, led to the restoration of normal cell growth pattern and senescence. Almost 100 percent of cervical cancer is positive for the presence of HPV virus. Future studies in this project are directed to identify human genes disrupted through HPV integration, and examine their role in the etiology of cervical cancer.

 

The ultimate aim of our research is to identify molecular targets for diagnosis and therapeutic intervention of cancer.

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

21980037. Rane NS, Sandhu AK, Zhawar VS, Kaur G, Popescu NC, Kandpal RP, Jhanwar-Uniyal M, Athwal RS, Restoration of senescence in breast and ovarian cancer cells following the transfer of the YAC carrying SEN6A gene located at 6q16.3. Cancer Genomics Proteomics 8:5(227-33)2011 Sep-Oct

20230879. Zhawar VK, Kaur G, deRiel JK, Kaur GP, Kandpal RP, Athwal RS, Novel spliced variants of ionotropic glutamate receptor GluR6 in normal human fibroblast and brain cells are transcribed by tissue specific promoters. Gene 459:1-2(1-10)2010 Jul 1

19789346. Liu J, Kaur G, Zhawar VK, Zimonjic DB, Popescu NC, Kandpal RP, Athwal RS, Role of SV40 integration site at chromosomal interval 1q21.1 in immortalized CRL2504 cells. Cancer Res 69:19(7819-25)2009 Oct 1

19382914. Liu J, Zhawar VK, Kaur G, Kaur GP, Deriel JK, Kandpal RP, Athwal RS, Chromosome 6 encoded RNaseT2 protein is a cell growth regulator. J Cell Mol Med 14:5(1146-55)2010 May

15558027. Kaur GP, Reddy DE, Zimonjic DB, de Riel JK, Athwal RS, Functional identification of a BAC clone from 16q24 carrying a senescence gene SEN16 for breast cancer cells. Oncogene 24:1(47-54)2005 Jan 6

10644999. Reddy DE, Keck CL, Popescu N, Athwal RS, Kaur GP, Identification of a YAC from 16q24 carrying a senescence gene for breast cancer cells. Oncogene 19:2(217-22)2000 Jan 13

10490846. Reddy DE, Sandhu AK, DeRiel JK, Athwal RS, Kaur GP, Identification of a gene at 16q24.3 that restores cellular senescence in immortal mammary tumor cells. Oncogene 18:36(5100-017)1999 Sep 9

9542531. Pidlaoan LV, Jin J, Sandhu AK, Athwal RS, Kunapuli SP, Colocalization of P2Y2 and P2Y6 receptor genes at human chromosome 11q13.3-14.1. Somat Cell Mol Genet 23:4(291-6)1997 Jul

8702478. Akbar GK, Dasari VR, Webb TE, Ayyanathan K, Pillarisetti K, Sandhu AK, Athwal RS, Daniel JL, Ashby B, Barnard EA, Kunapuli SP, Molecular cloning of a novel P2 purinoceptor from human erythroleukemia cells. J Biol Chem 271:31(18363-7)1996 Aug 2

9245338. Athwal RS, Kaur GP, Complementation Mapping in Microcell Hybrids: Localization of XRCC4 to 5q15-q21 Methods 9:1(12-9)1996 Feb

8579591. Ayyanathan K, Webbs TE, Sandhu AK, Athwal RS, Barnard EA, Kunapuli SP, Cloning and chromosomal localization of the human P2Y1 purinoceptor. Biochem Biophys Res Commun 218:3(783-8)1996 Jan 26

8570202. Sandhu AK, Kaur GP, Reddy DE, Rane NS, Athwal RS, A gene on 6q 14-21 restores senescence to immortal ovarian tumor cells. Oncogene 12:2(247-52)1996 Jan 18

8643996. Dasari VR, Sandhu AK, Mills DC, Athwal RS, Kunapuli SP, Mapping of the P2U purinergic receptor gene to human chromosome 11q 13.5-14.1. Somat Cell Mol Genet 22:1(75-9)1996 Jan

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