• DEPARTMENT:

          Biochemistry and Molecular Biology

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Surinder K. Batra, Ph.D.

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ACADEMIC DEGREES:
Medical/Graduate School:        NDRI, India
Residency/Fellowship Training: INRA, France
Post-doctoral Training:             Duke University Medical Center, NC

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Contact Name: Surinder K. Batra
Phone Number: 402-559-5455 (Office)
402-559-7754 (Lab)
e-mail address: sbatra@unmc.edu

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• GRANT SUPPORT (last 3 years):

CURRENT:

07/01/02-06/30/07	Principal Investigator (25% effort, 25% Salary) Molecular studies on MUC4 mucin gene National Institutes of Health Grant Number 2R01 CA 78950-5 Total Project Costs $1, 111,500
12/01/00-11/30/03	Principal Investigator (30% effort, 30% Salary) Genetically engineered multivalent single chain antibody constructs for cancer Department of Energy Grant Number DE-FG02-62024-A001 Total Project Costs $915,000
04/01/02-06/31/03	Principal Investigator (20% effort, 10% Salary; Director M.A. Hollingswroth Biological marker(s) for pancreatic cancer diagnosis National Institutes of Health, SPORE 1P50CA72712-01 Total Project Costs $152,077
01/01/03-12/31/04	Principal Investigator (10% effort, 0% Salary) Molecular studies on MIC-1/PDF gene Cattleman UNMC Eppley Cancer Center Total Project Costs $120,000
09/01/01-	Principal Investigator (1% effort, No Salary) Early diagnosis of pancreatic cancer Fraternal Orders of Eagles (Local and National Chapter) Total $6,200
03/01/99-	Principal Investigator (1% effort, No Salary), Bonnie Van Haitsma Memory Funds Eppley Institute, UNMC Early detection of genetic changes in hamster pancreatic cancer model Total Direct Cost $10, 000
07/01/98-06/30/03	Co-investigator (3% effort, No Salary, Michael Hollingsworth, PI) Center of Research Excellence in Glycobiology Nebraska Research Initiative Total Project Direct Costs $1,090,000
07/01/98-06/30/03	Co-investigator (3 % effort, No Salary; Angie Rizzino, Principal Investigator) Analysis of differential gene expression during differentiation and carcinogenesis Nebraska Research Initiative Total Project Direct Costs $1,426,000
07/01/99-06/01/03	Project Leader (3 % effort, No Salary; Ming-Fong Lin, Program Project Leader) Genetic changes during human prostate carcinogenesis NE Dept. of Health, LB595 Project Total Project Direct Costs $300,000
Past:
07/01/98-06/01/02	Principal Investigator (30% effort, 30% Salary) Molecular studies on MUC4 mucin gene National Cancer Institute National Institutes of Health Grant Number R01 CA 77466 Total Project Costs $743,650
04/01/01-06/30/02	Principal Investigator (Effort 2%; No salary) Radioimmunotherapy of prostate carcinomas. UNMC Seed Grant Total Project Direct Costs $ 30, 000
07/01/01-06/30/02	Co-Investigator (PI: Donald J. Buchsbaum) (Effort 3%; No salary) Multimodality treatment of pancreatic cancer National Institutes of Health, SPORE 1P50CA72712-01 Total Direct cost $50,000, ($19, 000 subcontract to SKB)
03/01/97-01/31/02	Co-Investigator (5 %; Salary 5 %) (PI: Michael A. Hollingsworth) Use of vasoactive pepetides to modify monoclonal antibody pharmacology National Institutes of Health SPORE 1P50CA72712-01 Total Project Costs $958,000
07/01/01-06/30/02	Principal Investigator (5% efforts, no Salary) Title: Regulation of MUC4 mucin promoter NE Department of Health LB506 Total project cost $40,000
03/01/99-02/28/01	Project Leader (5% effort, 5% salary; Margaret A. Tempero, Principal Investigator) Optimizing therapy of pancreatic adenocarcinomas with TALL-104 cells. Marc Lustgarten Foundation f or Pancreatic Research Total Project Costs $250,000
07/01/99-6/30/00	Principal Investigator (5% effort, 0% salary) Early genetic alterations during human pancreatic carinogenesis NE Department of Health LB506 Total Projects Costs $30,000
07/01/99-06/30/00	Co-investigator (3% effort, 0% salary; Ming-Fong Lin, Princiapal Investigator) Tyrosine phosphorylation in prostate cancer cells. NE Department of Health LB506 Total Project Costs $30,000
03/01/98-02/28/99	Principal Investigator (5% effort, no salary) Molecular studies on an amplified gene (PD2) in panreatic adenocarcinomas National Institutes of Health NIH SPORE Grant (PI: Margaret Tempero) Total Project Direct Costs $30,000
01/01/98-12/31/98	Principal Investigator (5% effort, no salary) Monoclonal antibodies against mutant EGF receptor NE Dept. of Health LB595 Seed Grant Total Project Direct Costs $29,9980
07/01/98-06/30/99	Co-investigator (5% effort, no salary; J.K. Vishwanatha, Principal Investigator) General alterations in oral cancer UNMC Translational Seed Grant Total Direct Costs $15,000
06/01/97-05/30/98	Principal Investigators: Surinder K. Batra and Margaret Tempero (5% effort) Human Monoclonal Antibodies Reactive with Tumor-Associated Antigens UNMC Translational Seed Grant Total Project Direct Costs $15,000
07/1/97-06/30/98	Co-investigator (5% effort, no salary; David Colcher, Principal Investigator) Human Monoclonal Antibodies for Cancer Therapy NE Dept. of Health LB595 Seed Total Project Direct Costs $29,920

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Chu, C.T., Everiss, K., Wikstrand, C.J., Batra, S.K., Kung, H.J., and Bigner, D.D. Receptor dimerization is not a factor in the signaling activity of a transforming variant epidermal growth factor receptor. Biochemical J., 324: 855-861, 1997.

Ashley, D.M., Sampson, J.H., Archer, G.E., Batra, S.K., Bigner, D.D., and Hale, L.P. A genetically modified allogeneic cellular vaccine generates MHC class I-restricted cytotoxic responses against tumor-associated antigens and protects against CNS tumor challenge. J. Neuro-Immunology. 78: 34-46, 1997.

Reist, C.J., Batra S.K., Bigner D.D and Zalutsky M.R. Radiolabeled monoclonal antibodies for targeting tumor-associated EGFRvIII. Nucl. Med. Biol., 24: 639-647, 1997.

Ashley, D.M., Batra, S.K., and Bigner D.D. Monoclonal antibodies to growth factors and growth factor receptors: their diagnostic and therapeutic potential in brain tumors. J. Neuro-oncol., 35: 259-273, 1997

Bigner, S.H., Batra, S. K., and Rasheed, A. Mechanisms of altered growth control: cytogenetics, oncogenes and suppressor genes. In Russell and Rubinstein’s Pathology of Tumors of the Nervous System, Sixth Edition, Vol 1, chapter 2, 47-82, 1998

Colcher, D., Pavlinkova G., Beresford, G., Booth B.J.M.,Choudhury A and Batra S.K. Pharmcokinetics and biodistribution of genetically-engineered antibodies. Quat. J. Nuclear Medicine., 42(4), 225-241, 1998.

Pavlinkova G., Beresford, G., Booth B.J.M., Batra S.K., and Colcher, D. Charge-modified single chain antibody constructs of CC49: generation, characterization, pharmacokinetic and biodistribution analysis. Nucl Med Biol, 26,27-34, 1999.

Schmidt B., Liu G., Moyer M.P., Hernberg, S.B., Sanger W., Batra S.K., and Pour M. Induction of adenocarcinoma from hamster islet cells treated with N-ntrosbis(2-oxoprppyl)amine in vitro. Carcinogenesis, 20, 317-324, 1999.

Colcher, D., Pavlinkova G., Beresford, G., Booth B.J., and Batra S.K.. Single chain antibodies in pancreatic cancer. Ann. N. Y. Acad. Sci., 880:263-80, 1999.

Beresford, G.,Pavlinkova G., Booth B.J.M., Batra S.K., and Colcher, D. Binding characteristics and tumor targeting of a covalently-linked divalent CC49 single-chain antibody. Int. J. Cancer, 81: 911-7, 1999.

Colcher, D., Goel A., Pavlinkova G.,G., Booth B.J.M.,and Batra S.K. Effects of genetic engineering on the pharmcokinetics of antibodies. Quat. J. Nuclear Medicine., 43, 132-9, 1999.

Pavlinkova G., Beresford, G., Booth B.J.M., Batra S.K., and Colcher, D. Radioimmunotherapy of human colon cancer xenografts using a di meric single-chain Fv antibody construct. Clin. Cancer Res., 5, 2613-2619, 1999.

Pavlinkova G., Beresford, G., Booth B.J.M., Batra S.K., and Colcher, D. Pharmacokinetics and biodistribution of engineered scFv constructs of MAb CC49 in colon carcinoma xenograft system. J. Nuclear Medicine, 40, 1536-46, 1999.

Matsuzaki, H., Schmied, B.M., Ulrich, A., Batra, S.K., And Pour, PM. In vitro induction of giant cell tumors from cultured hamster islets treated with BOP. American J. Pathology, 156, 439-443, 2000.

Schmied, T B., Liu, G., Matsuzaki H., Ulrich A., Hernberg, S.B., Moyer, M. P., Weide L., Murphy L., Batra, S.K., and Pour, P. Differentiation of islet cells in cells in long-term culture. Pancreas, 20(4):337-47, 2000.

Schmied, T B., Ulrich, A.B., Hosei, M., El-metwally T.H., Ding X., Fernandes M.E., Adrian T.E, Chaney W.G., Batra, S.K., and Pour, P. M. Biological instability of pancreatic cancer xenografts in the nude mice. Carcinogenesis, 21:1121-7, 2000

Goel, A.,Colcher D., Beresford, G.W., Pavlinkova, G., Booth, B.J., Baranowska-kortylewicz, N., and Batra, S.K. Divalent forms of CC49 single-chain antibody constructs in Pichia pastoris: expression, purification, and characterization. J. Biochem.127: 829-36, 2000.

Choudhury, A., Moniaux, N., Reid C. J., Hollingsworth M.A., Aubert, J.P., and Batra, S.K. Human Pancreatic tumor-associated mucin MUC4 cDNA and its derivatives. J. Biochem 128, 233 - 243, 2000.

Moniaux, N., Escande, F., Batra, S.K., Porchet, N., Laine, A., and Aubert, J.-P. Alternative splicing generates a family of both soluble and membrane-associated MUC4 apomucins. Eur. J. Biochem. 267, 4536-44, 2000.

Pavlinkova,G., Colcher, D., Booth, B.J.,Goel A., and Batra, S.K. Pharmacokinetics and biodistribution of a light chain shuffled CC49 single-chain Fv antibody construct. Cancer Immunology Immunotherapy, 49: 267-75 2000.

Goel, A., Colcher D., Koo J.S.,. Booth, B.J., Pavlinkova, G., and Batra, S.K. Relative position of the hexa-histidine tag effects binding properties of a tumor-associated single-chain Fv construct. Biochem Biophys.Acta, 1519, 13-20, 2000.

Choudhury, A., Singh, R., Moniaux, N., El-Metwally, T., Aubert, J.-P., and Batra, S.K. Retinoic acid dependent transforming growth factor-β-mediated induction of MUC4 mucin expression in human pancreatic tumor cells follows retinoic acid receptor-α signaling pathway. J. Biol. Chem., 275, 33929-33936, 2000.

Ulrich, A.B., Schmied, B.M., Matsuzaki, H. El-Metwally, T., Moyer, M.P., Ricordi, C. Adrian, T.E. Batra, S.K., Pour, P.M. Establishment of human pancreatic ductal cells in a long term culture. Pancreas, 21(4):358-68 , 2000.

Goel, A., Colcher D., Baranowska-kortylewicz., Augstine, S., Booth, B.J., Pavlinkova, G., and Batra, S.K. Genetically-engineered tetravalent single-chain Fv of the pancarcinoma monoclonal antibody CC49: improved biodistribution and potential for therapeutic application . Cancer Research, 60, 6964-6971, 2000.

Schmied, T B., Ulrich, A.B., Hosei, M., Ding X., Ricordi C., Weide L., Moyer M.P., Batra S.K., Adrian T.E., and Pour, P. M. Transdifferentiation of human islets in long term culture. Differentiation, 66, 173-180, 2000.

Ringel J., Jesnowski, R., Schmidt, C., Köhler, H.J., Ringel, J., Batra, S.K., and Löhr M. CD44 in normal human pancreas and pancreatic carcinoma cell lines. Teratog, Carcinog Mutagen, 21, 97-106, 2001.

Choudhury, A., Moniaux, N., Ringel, J., King, J., Moore E., Aubert, J.P., and Batra S.K. Alternate splicing at the 3=-end of the human pancreatic tumor-associated mucin MUC4 cDNA. Terat, Carcinog , Mutagen 21, 83-96,2001.

Goel, A., Augustine, S., Baranowska-Kortylewicz, J., Colcher, D.,Booth, B.J.M., Pavlinkova, G., Tempero, M., and Batra, S.K. Single-dose versus fractionated radioimmunotherapy of human colon carcinoma xenografts using ¹³¹i-labeled multivalent cc49 single-chain Fvs. Clinical Cancer Research,7, 175-184, 2001.

Goel, A and Batra S.K. Antibody constructs for radioimmunodiagnosis and treatment of human pancreatic cancer. Teratog, Carcinog Mutagen, 21, 45-58, 2001.

Moniaux, N., Porchet N., Aubert J.P and Batra S.K.  Structural organization and classification of human mucin genes (MUC).  Front Biosc, 6, d1192-1206, 2001.

Silverman, H.S., Parry, S., Sutton-smith M., Burdick, M. D, Mcdermott, K., Reid C.J., Batra S.K., Morris, H.R., Hollingsworth M, A, Dell, A., and Harris, A.  In vivo glycosylation of mucin tandem repeats.  Glycobiology, 11,459-471, 2001.

Karan, D., Johansson S.l., Lin, M.F., and Batra S.K.  Expression of TAG-72 (Tumor-Associated Glycoprotein-72) antigen in prostatic Adenocarcinomas.  Oncology Report, 8:1123-1126, 2001

Jain, M., Karan D., Batra S.K., and Varshney G.C.  Mucins in protozoan parasites.  Front Biosc, 6, d1276-1283, 2001.

Schmied BM, Ulrich A, Matsuzaki H, Ding X, Ricordi C, Weide L, Moyer MP, Batra SK, Adrian TE, Pour PM.  Transdifferentiation of human islet cells in a long-term culture. Pancreas, 23, 157-171, 2001.

Wittel, U., Goel A, Varshney G.C and Batra S.K.  Mucin antibodies-new tools in diagnosis and therapy of cancer.  Fron Bios, 6, d1296-1310, 2001

Batra S.K., Goel,A., Pavlinkova, G., and Colcher, D. Monoclonal antibody targeted radionuclide therapy. In Targeted Therapy for Cancer, edited by Syrigos, K.N., and Harington, K.J; Oxford University Press (London U.K.), 2001.

Goel, A., Baranowska-kortylewicz J., Hinrichs S.H., Wisecarver J., Pavlinkova, G., Augstine, S., Colcher D., and Batra, S.K.  .  99mTc-labeled divalent and tetravalent cc49 single-chain fv's: novel imaging agents for rapid in vivo localization of human colon carcinoma J. Nuclear Medicine, 42, 1519-27, 2001. 

Pavlinkova, G., Colcher, D., Booth, B.J., Goel A., and Batra, S.K.  Immunogenicity and antigen binding of CC49 single chain Fv antibody constructs.  Int. J. Cancer, 94 (October), 10 pages, in press, 2001.

Andrianifahanana, M., Moniaux, N., Ringel, J., A., Schmied, B.M., Hollingsworth, M.A., Aubert, J.P., and Batra, S.K.  Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: A potential role of MUC4 as a tumor marker of diagnostic significance.  Clin Can Res, in press, 2001

Muscarella P., Knobloch T.J., Ulrich A.B., Casto B.C., Moniaux N., Wittel U.A., Melvin W.S., Pour P.M., Song H., Gold B., Batra S.K, and Weghorst C.M.  Identification and sequencing of the Syrian Golden Hamster (Mesocricetus auratus) p16INK4a and p15INK4b cDNAs and their homozygous gene deletion in cheek pouch and pancreatic tumor cell lines.  Gene, in press, 2001.

Karan D, Lin MF and Batra SK.  Molecular genetic changes in human prostatic adenocarcinomas. Int J. Oncology, in press, 2001 

Karan D, Schmied BJ, Dave BJ, Wittel UA, Lin MF and Batra SK.  Decreased androgen-responsive growth of human prostate cancer is associated with increased genetic alterations.  Clin Canc Res, in press, November 2001.

Igawa, T., Lin, F.n., Lee, M.s., Karan, D., Batra S.K., and Lin, M.F.  Establishment and characterization of androgen-unresponsive cancer cell LNCaP subline model.  Prostate, 50, 222-35, 2002.

Khorrami, A.M., Choudhury, A., Andrianifahanana, M., Varshney G.C., Bhattacharyya, S.N., Hollingsworth, M.A., Kaufman, B, and Batra S.K.  Purification and characterization of a human pancreatic adenocarcinoma mucin.  J. Biochem., 131, 21-29, 2002.

Batra S.K., Jain M., Chauhan S.C., Wittel, U.A., and Colcher D. Pharmacokinetics and biodistribution of genetically engineered antibodies. Curr. Opin. Biotech., 13 (6), 13, 603-6082002. 

Karan D., Johansson S.L., Lin M.F., and Batra SK.  Current status of molecular genetic changes in human prostatic adenocarcinomas.  Int. J. Cancer, 103, 285-293, 2003

Batra ,S.K., Goel, A., Pavlinkova G and Colcher D. Monoclonal antibody targeted radionuclide therapy. In A Targeted therapy for cancer. Eds: Syrigos K.N and Harrington K.J., Oxford University Press (London, U.K.), in press, 2003.

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Uwe Wittel, M.D. Resident from April 2002
(2000-2001) Freiburg, Germany

Girsh C. Varshney, Ph.D. Moved to join as an assistant director on Feb. 1, 2001
(2000-01)Institute of Microbial Technology Chandigarh, India

Jeorge Ringel, M.D. moving to join on March 1, 2001 the faculty
(1999-01) Universität Heidelberg, Theodor Kutzer Ufer 68135 Mannheim, Germany

Apolina Goel, Ph.D. Senior Post-doctoral Fellow
(1998-00) Mayo Clinics, Rochester, MN

Bruno Schmied, M.D. Resident
(1997-99) Department of Visceral and Transplantaion Surgery
Insel Hospital, Switzerland

Amit Choudhury, Ph.D, Research Associate
(1997-00) Mayo Clinics, Rochester, MN

Tarek H. EI-Metwally, Ph.D Associate Professor
(1999) University of Egypt, Egypt.

Xuanmin He, M.D., Ph.D. Senior Scientist
(1992-94) Pharmagen, San Diago, CA

Ja Seok Koo, Ph.D. Staff Fellow
(1993-95) NIEHS, NC

Grit Faulman, MD Resident
(2000) Universität Heidelberg, Theodor Kutzer Ufer, Germany

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• CURRENT RESEARCH PROJECTS

The major focus of Dr. Batra’s research program is centered in the area of pancreatic cancer, which is becoming an international problem because of its increasing global incidence.  Mucins, in general, have been implicated in the pathogenesis of benign and malignant diseases of secretory epithelial cells; however, the molecular basis of the alterations that occur in mucins during different diseases is poorly understood. In pancreatic cancer, Dr. Batra’s research is making a pioneering attempt to investigate and evaluate the potential diagnostic and therapeutic potentials of a novel MUC4 mucin that they have purified, cloned, and characterized. His group has shown that the MUC4 expression occurs in peripheral blood mononuclear cells (PBMC) of pancreatic cancer patients compared to no expression in PBMC of normal human and other cancer patients. Furthermore, expression of MUC4 in normal human pancreas and/or chronic pancreatitis is not detectable, but it is highly expressed in pancreatic tumor cells. Also, expression of MUC4, in human pancreatic tumor cells, is dependent on serum and several serum constituents particularly all-trans-retinoic acid (RA). The RA-mediated increase in the level of the MUC4 transcript coincided with an increased expression of transforming growth factor-β2 (TGF-β2) transcript.  These in vitro studies appear to be highly relevant to the expression of MUC4 and TGF-β2 in vivo. Unpublished results from our laboratory show a direct relation between MUC4 expression by pancreatic adenocarcinoma cells and metastasis from the following studies: 1) The HPAF/CD18 pancreatic tumor cells, when grown orthotopically in mice, expressed high levels of MUC4 and showed distant lymph node metastasis. 2) A serial orthotopic and subcutaneous implantations were performed producing primary pancreatic tumors as well as lymph node, colon, and diaphragm metastases of another established pancreatic tumor line SW1990. In this metastatic model, MUC4 expression was directly correlated with metastasis. 3) A stable knockout of MUC4 expression HPAF/CD18 blocked lymph node metastasis. Thus, we believe that MUC4 plays a significant role in the progression of pancreatic cancer and understanding the role of MUC4 variants could bring a new approach to limit metastasis formation among the patient with pancreatic cancer therefore largely improve the survival rate after resection. 

Besides, tumor-associated glycoprotein (TAG72) mucin is being used in his group as a target for radioimmunotherapy.  In this direction, Dr. Batra and his colleagues have engineered for the first time multivalent anti-TAG72 single chain antibody constructs which have shown very promising results or cancer therapy and imaging.  Thus, mucin expression, particularly MUC4, in pancreatic tumors or PBMC of pancreatic cancer patients suggests a link between regulation of its expression and cellular alterations involved in the oncogenic and metastatic process. Such gene or gene probes emerging from Dr. Batra’s laboratory might provide useful tools for the diagnosis and therapy of pancreatic carcinomas.

In addition, Dr. Batra’s lab is also developing new targets for advanced prostate cancer. His group has identified several specific genetic alterations and differentially-expressed genes that are being explored as marker/or target for the progression of prostate cancer.

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• SPECIALIZED LABORATORY RESEARCH RESOURCES:

Mucin analysis; Antibody Engineering, Gene-Detection Analysis; Radioimmunotherapy.

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