Biochemistry/Molecular Biology, Urological Surgery, and Eppley Institute

Ming-Fong Lin, Ph.D., Professor

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ACADEMIC DEGREES:

2/83	Ph.D., Roswell Park Memorial Institute Graduate Division, SUNY, Buffalo, NY
1988	Assistant Professor, Dept. of Urology, and Basic Science Division, USC Comprehensive Cancer Center, USC, Los Angeles, CA
1995	Associate Professor, Dept. of Biochem./Mol. Biol. & Surgery/Urology, and Eppley Cancer Institute, UNMC, Omaha, NE
1996-present	Coordinator, UNMC Prostate Cancer Research Focus Group, Omaha, NE
2000-present	Professor, Departments of Biochemistry/Molecular Biology and Surgery/Urology, and Eppley Cancer Institute, UNMC, Omaha, NE

   

PROFESSIONAL

1995	Member, MBY-7 Molecular Biology Study Section, US Army Breast Cancer Program
1996-97	Reviewer, VA Merit Grants, Department of Veterans Affairs
10/1998	Ad Hoc Member, Biochemical Endocrinology Study Section, NIH
01/99 present	Ad Hoc Member & Member, Tumor Biochemistry and Endocrinology Study Section, ACS
07/1999	Member, Epidemiology and Disease Control-2 Special Review Panel in Prostate Cancer, NIH
08/2000	Member, NIDDK Diseases Special Emphasis Panel, ZDK1 GRB-5 (O1), NIH

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Contact Name: Ming-Fong Lin, Ph.D.
Phone Number: 402-559-6658
e-mail address: mlin@unmc.edu

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• GRANT SUPPORT (last 3 years):

"Signaling in Androgen-Refractory Prostate Cancer"
PI: Ming-Fong Lin, Ph.D., NCI, R01 CA88184, 7/1/2000 - 6/30/2005
Investigate the functional role of tyrosine phosphorylation signaling in androgen-independent growth of human prostate cancer cells.

"Steroid Regulation of Human Prostate Cancer Cells"
PI: Ming-Fong Lin, Ph.D., NCI, R01 CA72274, 7/1/1996 - 6/30/2001
Investigate the functional role of cellular prostatic acid phosphatase in prostate cell growth regulation.

"Biology of Hormone Refractory Human Prostate Cancer"
PI: Ming-Fong Lin, Ph.D., LB595/Eppley Cancer Center, Program Project seed grant, 7/1/1999 - 6/30/2002
The long term objective of this project is to develop and establish a prostate cancer research program at UNMC

"Analysis of Differential Gene Expression During Differentiation and Carcinogenesis by DNA Chip Technology"
Co-investigator: Ming-Fong Lin, Ph.D. (PI: Angie Rizzino, Ph.D.), Nebraska Research Initiative, Research Grant, 7/1/1998 - 6/30/2002
The goal is to establish a UNMC Functional Genomics/DNA Array Program.

"Establishment of a DNA Array Facility at UNMC"
Co-Investigator: Ming-Fong Lin, Ph.D. (PI: Michael A. Hollingsworth, Ph.D.), NCI, CA79580S, 9/1/1999 - 8/31/2000
This grant budget is only for obtaining additional equipments for the above described Functional Genomics Program at UNMC.

"Tyrosine phosphorylation in Prostate Cancer Cells"
PI: Ming-Fong Lin, Ph.D., LB506-NE DHHS, #2000-19, 7/1/1999-6/30/2000
This proposal studied tyrosine phosphorylation signaling in growth regulation of human prostate cancer cells.

"Biology of Hormone Refractory Human Prostate Cancer"
PI: Ming-Fong Lin, Ph.D., Co-I: Judith K. Christman, Ph.D., Richard G. MacDonald, Ph.D.
Eppley Cancer Center P01 Program Project Seed Grant, 7/1/1998-6/30/1999
The seed grant was used to support new initiatives involving in prostate cancer research.

"Role of Prostatic Acid Phosphatase in Prostate Cancer"
PI: Ming-Fong Lin, Ph.D., LB506-NE DHHS, #98-29, 7/1/1997-6/30/1998
This funding supported studies in understanding the functional role of cellular PAcP.

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• PUBLICATIONS (selected):

Spruck CH III, Gonzalez-Zulueta M, Shibata A, Simoneau AR, Lin M-F, Gonzales F, Tsai YC, and Jones PA. p16 gene in uncultured tumours. Nature 370:183-184, 1994.

Lin M-F, Kawachi M, Stallcup M, Grunberg S, and Lin FF. Growth inhibition on androgen!insensitive human prostate carcinoma cells by a 19-Norsteroid derivative agent, mifepristone. The Prostate 26:194-204,1995.

Lin, M-F, Meng, TC, Rao, PS, Chang, CS, Schonthal, AH, and Lin, FF. Expression of human prostatic acid phosphatase correlates with androgen stimulated cell proliferation in prostate cancer cell lines. J. Biol. Chem. 273:5939-5947, 1998.

Meng, TC, and Lin, M-F. Tyrosine phosphorylation of c-ErbB-2 is regulated by the cellular form of prostatic acid phosphatase in human prostate cancer cells. J. Biol. Chem. 273:22096-22104, 1998.

Yeh, SY, Lin, HK, Kang, HY, Thin, TH, Lin, M-F, and Chang, CS. From HER2/Neu signal cascade to androgen receptor and its coactivators: A novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells. Proc. Natl. Acad. Sci. USA 96: 5458-5463, 1999.

Zelivianski, S, Larson, C, Seberger, J, Taylor, R, and Lin, M-F. Expression of human prostatic acid phosphatase is regulated by upstream negative and positive elements. Biochem. Biophys. Acta 1491: 123-132, 2000.

Zelivianski, S, Dean, J, Madhavan, D, Lin, FF, and Lin, M-F. Expression of receptor protein tyrosine phosphatase  mRNA in human prostate cancer cell lines. Mol. Cellu. Biochem. 208:11-18, 2000.

Meng, TC, Lee, MS, and Lin, M-F. Interaction between protein tyrosine phosphatase and protein tyrosine kinase is involved in androgen-promoted growth of human prostate cancer cells. Oncogene 19:2664-2677, 2000.

Lin, M-F, Lee, MS, Garcia-Arenas, R, and Lin, FF. Differential responsiveness of prostatic acid phosphatase and prostate-specific antigen mRNA to androgen in prostate cancer cells. Cell Biology International 24:681-689, 2000.

Zhang, XQ, Lee, MS, Zelivianski, S, and Lin, MF. Characterization of a prostate-specific tyrosine phosphatase by mutagenesis and expression in human prostate cancer cells. J. Biol. Chem. 276: 2544-2550, 2001.

Zelivanski, S, Verni, M, Moore, C, Kondrikov, D, Taylor, R, and Lin, M-F.  Multipathyways for transdifferentiation of human prostate cancer cells into neuroendocrine-like phenotype.  Biochem. Biophys. Acta 1539: 28-43, 2001.

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• PREVIOUS GRADUATE STUDENTS/POST-DOCTORAL FELLOWS (present location):

Previous graduate student at UNMC
Tsu-Ching Meng, Department of Biochemistry and Molecular Biology, COM
8/1995 - 8/1999, Currently: Post-doctoral Fellow, Cold Spring Harbor Laboratory, NY

Previous Postdoctoral Fellow/Urology Fellow/Residency
UNMC
Prathibha Rao, Ph.D., Department of Biochemistry and Molecular Biology
1/1997 - 3/1998, Currently: Pharmacia & Upjohn company
P. James Seberger, Ph.D., Department of Biochemistry and Molecular Biology
12/1998 - 7/1999, Currently: Medical student at the UNMC College of Medicine
USC
Seth Lerner, M.D., Uro-Oncology Fellow
9/1990 - 6/1991, Co-Supervisor with Dr. Peter Jones, Currently: Assistant Professor, Department of Urology, Baylor Medical College, Houston, TX.
Mark Kawachi, M.D., Uro-Oncology Fellow
7/1991 - 6/1992, Currently: Associate Professor, Department of Urologic Oncology, City of Hope National Medical Center, Duarte, CA.

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• CURRENT RESEARCH PROJECTS:

Translational Research in Human Prostate Cancer
Our research interest is to understand the molecular mechanisms that regulate the progression of prostate cancer for developing improved treatments for this disease. Currently, we focus our efforts on advanced prostate cancer. This is because that the treatment of this patient population is limited. Novel modalities of therapy are urgently needed. Our research projects are briefly described as follows:

i) We are investigating the molecular mechanism by which human prostate cancer cells can grow in the androgen-depleted environment. We have discovered an enzyme specific to prostate cells is involved in regulating androgen-responsive cell proliferation. We can convert cells from the androgen-insensitive to androgen-responsive phenotype by expressing this enzyme in those cancer cells. Furthermore, this enzyme can directly suppress tumor development. These findings could lead to the development of new therapies to control advanced prostate cancer.

ii) Clinical reports clearly show that in advanced tumors, a sub-population of cancer cells, i.e., neuroendocrine (NE) cells, arises. This new cell population may be involved in hormone-refractory growth of cancer cells. We are characterizing our newly established NE-like cells for their functional role in cancer progression. These cells can then be utilized to develop new strategies for treating advanced hormone-refractory cancer patients.

iii) Our lab also are involved in developing novel reagents for expressing genes specifically in prostate cancer cells. These reagents can be used potentially to formulate a specific, effective gene therapy protocol for treating all prostate cancer patients.

iv) Another line of research in Dr. Lin=s lab is investigating new approaches including the discovery of new drugs and development of pro-drugs. We discovered previously that mifepristone, also known as RU486, can suppress hormone-refractory human prostate tumor growth in a xenograft animal model. An anecdotal result was observed clinically. Further clinical trials may provide us with additional information in its efficacy.

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• SPECIALIZED LABORATORY/CLINICAL RESEARCH RESOURCES:

We have established various human prostate cancer cell models, primary cultures, xenograft animal models.