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Uma Raju, Ph.D.

Present Title & Affiliation

Primary Appointment

Assistant Professor, Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

More than 50% of cancer patients undergo chemo-radiation therapy as part of their treatment regimen for upper aero-digestive tract cancers, such as head and neck and lung cancers. However, the cure rate is still low and there is a need for novel treatment strategies to improve treatment outcome. My research interest is to test the hypothesis that targeting molecules whose functions are well regulated in normal cells but deregulated in cancer cells will improve tumor response with a better therapeutic gain. My investigation include preclinical evaluation of several molecularly targeted agents: (1) cetuximab, an anti- EGFR antibody, (2) celecoxib, an inhibitor of COX-2, (3) flavopiridol, an inhibitor of cdks, (4) BMS-599626 and BMS-690514, pan-EGFR family inhibitors, (5) XL-844, an inhibitor of Chk kinases, (6) Dasatinib (BMS-354825), an inhibitor of Src family kinases, (7) XL-228, an inhibitor of cSrc, IGF-1R and aurora kinases, (8) IMC-A12, an anti-IGF-1R antibody,  (9) Cilengitide, an inhibitor of two of the integrins, and (10) EMD1214063, an inhibitor of c-Met. The experimental cancer model systems used in these studies comprised many responders and non-responders to the above mentioned agents in combination with radiation or chemotherapy. Using these systems identification of markers of response/resistance to therapy is ongoing through profiling studies by proteomics and genomics. My focus is mainly on two sets of factors: (1) identification of cellular proteins and/pathways in DNA repair that are responsible for the resistant phenotype of cancer cells and (2) characterization of cancer stem cell markers that are involved in the resistance as well as recurrence and metastatic spread.

Education & Training

Degree-Granting Education

1982 Madurai Kamaraj University, Madurai, India, PHD, Neurophysiology and Circadian Rhythms
1976 Madurai University, Madurai, India, MS, Zoology
1974 Madurai University, Madurai, India, BS, Biology and Chemistry

Experience/Service

Academic Appointments

Instructor, Department of Experimental Radiation Oncology, Division of Radiation Oncology, UT M. D. Anderson Cancer Center, Houston, TX, 1/2002-3/2005
Research Associate, Department of Experimental Radiation Oncology, Division of Radiation Oncology, UT M. D. Anderson Cancer Center, Houston, TX, 9/2000-12/2001

Selected Publications

Peer-Reviewed Original Research Articles

1. Matsumoto F, Valdecanas DN, Mason KA, Milas L, Ang KK, Raju U. The impact of timing of EGFR and IGF-1R inhibition for sensitizing head and neck cancer to radiation. Anticancer Research 32(8):3029-35, 2012.
2. Torres MA, Raju U, Molkentine D, Riesterer O, Milas L, Ang KK. AC480, formerly MS-599626, a pan Her inhibitor, enhances radiosensitivity and radioresponse of head and neck squamous cell carcinoma cells in vitro and in vivo. Invest New Drugs 29(4):554-61, 8/2011. e-Pub 2/2/2010. PMID: 20119866.
3. Skvortsova I, Skvortsov S, Raju U, Stasyk T, Riesterer O, Schottdorf EM, Popper BA, Schiestl B, Eichberger P, Debbage P, Neher A, Bonn GK, Huber LA, Milas L, Lukas P. Epithelial-to-mesenchymal transition and c-myc expression are the determinants of cetuximab-induced enhancement of squamous cell carcinoma radioresponse. Radiother Oncol 96(1):108-15, 7/2010. e-Pub 5/5/2010. PMID: 20451273.
4. Skvortsova I, Skvortsov S, Stasyk T, Raju U, Popper BA, Schiestl B, von Guggenberg E, Neher A, Bonn GK, Huber LA, Lukas P. Intracellular signaling pathways regulating radioresistance of human prostate carcinoma cells. Proteomics 8(21):4521-33, 11/2008. e-Pub 9/2008. PMID: 18821526.
5. Dittmann KH, Mayer C, Ohneseit PA, Raju U, Andratschke NH, Milas L. Celecoxib induced tumor cell radiosensitization by inhibiting radiation induced nuclear EGFR transport and DNA-repair: a COX-2 independent mechanism. Int Journal Radiat Oncol Biol Physics 70(1):203-212, 1/2008. e-Pub 8/2007.
6. Dittmann KH, Mayer C, Ohneseit PA, Raju R, Andratschke NH, Milas L, Rodemann HP. The double-stranded RNA-activated protein kinase mediates radiation resistance in mouse embryo fibroblasts through nuclear factor kappaB and Akt activation. Int J Radiat Oncol Biol Phy 1(70):203-213, 1/2008. e-Pub 11/2007.
7. Wiedenmann N, Koto M, Raju U, Milas L, Mason KA. Modulation of tumor radiation response with G3139, a bcl-2 antisense oligonucleotide. Invest New Drugs 25(5):411-416, 10/2007. e-Pub 5/11/2007. PMID: 17492397.
8. von Holzen U, Pataer A, Raju U, Bocangel D, Vorburger SA, Liu Y, Lu X, Roth JA, Aggarwal BB, Barber GN, Keyomarsi K, Hunt KK, Swisher SG. The double-stranded RNA-activated protein kinase mediates radiation resistance in mouse embryo fibroblasts through nuclear factor kappaB and Akt activation. Clin Cancer Res 13(20):6032-9, 10/2007. PMID: 17947465.
9. Apisarnthanarax S, Alauddin MM, Mourtada F, Ariga H, Raju U, Mawlawi O, Han D, Bornmann WG, Ajani JA, Milas L, Gelovani JG, Chao KS. Early detection of chemoradioresponse in esophageal carcinoma by 3'-deoxy-3'-3H-fluorothymidine using preclinical tumor models. Clin Cancer Res 12(15):4590-7, 8/2006. PMID: 16899606.
10. Raju U, Ariga H, Koto M, Lu X, Pickett J, Valdecanas D, Mason KA, Milas L. Improvement of esophageal adenocarcinoma cell and xenograft responses to radiation by targeting cyclin-dependent kinases. Radiother Oncol 80(2):185-191, 8/2006. PMID: 16905211.
11. Milas L, Raju U, Liao Z, Ajani J. Targeting molecular determinants of tumor chemo-radioresistance. Semin Oncol 32(6 Suppl 9):S78-81, 12/2005. PMID: 16399438.
12. Raju U, Ariga H, Dittmann K, Nakata E, Ang KK, Milas L. Inhibition of DNA repair as a mechanism of enhanced radioresponse of head and neck carcinoma cells by a selective cyclooxygenase-2 inhibitor, celecoxib. Int J Radiat Oncol Biol Phys 63(2):520-8, 10/2005. PMID: 16168844.
13. Ismail SM, Puppi M, Prithivirajsingh S, Munshi A, Raju U, Meyn RE, Buchholz TA, Story MD, Brock WA, Milas L, Thames HD, Stevens CW. Predicting radiosensitivity using DNA end-binding complex analysis. Clin Cancer Res 10(4):1226-34, 2/2004. PMID: 14977819.
14. Raju U, Yeung SJ, Eskin A. Involvement of proteins in light resetting ocular circadian oscillators of Aplysia. Am J Physiol 258(1 Pt 2):R256-62, 1990. PMID: 2154135.

Book Chapters

1. Liao Z, Raju U, Mason K, Milas L. Cyclo-Oxygenase-2 enzyme and its inhibition in tumor growth and therapy. In: Cancer Drug Discovery and Development. Humana Press Inc., 2005.

Grant & Contract Support

Title: Pre-clinical evaluation of a combination therapy with cilengitide, erbitux and radiation in the treatment of human solid cancers
Funding Source: EMD Serono Merck
Role: Principal Investigator
Duration: 1/1/2012 - 12/31/2012
 
Title: Targeting C-Met signaling to improve tumor response to radiation
Funding Source: EMD Serono Merck
Role: Principal Investigator
Duration: 11/15/2011 - 11/14/2012
 
Title: Selective Enhancement of Tumor Response by Inhibiting EGFR and IGR-1R Pathways
Funding Source: NIH/NCI
Role: Co-Investigator
Principal Investigator: Ang
Duration: 9/1/2011 - 5/31/2016
 
Title: Pre-clinical evaluation of a combination therapy with cilengitide, an inhibitor of integrins, and radiation in the treatment of human solid cancers
Funding Source: EMD Serono Merck
Role: Principal Investigator
Duration: 12/10/2009 - 12/31/2011
 
Title: Pre-clinical evaluation of a novel combination therapy with Dasatinib (BMS-354825), C225 and radiation in the treatment of human head and neck squamous cell carcinomas
Funding Source: Bristol-Myers Squibb
Role: Principal Investigator
Duration: 11/29/2007 - 11/30/2009
 
Title: Effect of EXEL-9844, a Chk1 and Chk2 Inhibitor, on Radiosensitivity of Murine and Human Cancer Cells
Funding Source: Exelixis Inc.
Role: Principal Investigator
Duration: 8/10/2004 - 8/31/2005
 
Title: Extension of Radiotherapy Research - Proj 4: Selective Molecular Targeted Combined Therapy
Funding Source: NIH/NCI
Role: Co-Investigator
Principal Investigator: Ang
Duration: 4/1/2004 - 5/31/2011
 
Title: Preclinical evaluation of Afatinib (BIBW2992) given with radiation and chemotherapy in human head and neck squamous cell carcinoma models
Funding Source: Boehringer-Ingelheim
Role: Co-Investigator
Principal Investigator: Ang

Last updated: 2/18/2013