Research Faculty

Address
630 West 168th Street
VC 14-215
New York, NY 10032

Phone: 212-305-6739
Fax: 212-305-2301

hhh1@cumc.columbia.edu
Education and Training
1981 B.A. Physics and Chemistry, New York University
1985 M.D. New York Medical College


Affiliations
Herbert Irving Cancer Center
Breast Program

Collaborations
Ramon Parsons, Mary Beth Terry…
Hanina Hibshoosh, M.D.
Professor Of Clinical Pathology and Cell Biology
Research Summary

My two main areas of interest have been and are breast molecular carcinogenesis and research infrastructure development.

I have engaged in a wide range of studies involving molecular carcinogenesis with emphasis on breast cancer. These include participating(led by Ramon Parsons) in the discovery and characterization of the PTEN tumor suppressor gene, role of PTEN in basal breast cancer and BRCA1 related cancers, role of PDK1 in breast cancer, PTEN signature and Stathmin as a pathway activation marker as well as most recently identification of PTEN long(a secreted form of PTEN). I participated in the identification and characterization of a number of other tumor suppressor genes related to breast cancer including Protocadherin 8, BAF-180, and Beclin-1/ autophagy.

In addition, in collaboration with Marilie Gammon and Mary Beth Terry I carried out a series of large scale studies (Long Island Breast Cancer Study Project/New Jersey breast project… ) focused on the molecular epidemiology of breast cancer.

In the research infrastructure development front I am the founding Director (1998/currently director since June 2011) of the Molecular Pathology Shared Resource (MPSR) of The Herbert Irving Comprehensive Cancer Center of Columbia University whose aim is to facilitate tissue based cancer research (for details see http://www.hiccc.columbia.edu/research/sharedresources/molecular).

The MPSR enables research through three service lines, the first, a histology service; the second, a traditional tumor banking service; and the third, is known as the macromolecule platform/next generation tumor banking service. This is the largest shared resource of the cancer center. We currently service in excess of 379 unique investigators at Columbia University and in the past 5 years have fulfilled in excess of 17,000 requests for tissue based testing with our 11 full time employees. Beyond routine and specialized histology, immunohistochemistry, tissue micro-array construction we offer whole slide scanning storage and analysis, project management, and tumor banking operations as well next generation banking where tumors are systematically characterized for diagnosis, purity, viability, and DNA and RNA extracted and linked to clinical data and future research results. This creates a large scale and robust platform that reduces barriers to research in the genomic era and enables collaboration efficiently. Furthermore we offer molecular biology services that prepare analytes for any multi-omic interrogation including, expression array, epigenetic studies, micro RNA, full exome, RNAseq or whole genome sequencing or protein for RPPA. The MPSR has seen explosive growth during the past 14 years. The facility’s ever expanding capacity is a testimony to the high quality, efficiency, value add proposition, wide range and scalability of the services it provides.

I am also the director of the Tumor Bank at the Herbert Irving Comprehensive Cancer Center of Columbia University.

Lastly, I am the reference breast pathologist to the Breast Cancer Family Registry of New York. The Metropolitan New York Registry is a registry of families with a history of breast and/or ovarian cancer. The data and biospecimens donated by more than 8,000 high-risk families are being used by cancer researchers to identify new avenues for prevention, detection and treatment of breast cancer. With the help of thousands of families around the world - possibly including yours - the Registry is contributing to our growing understanding of breast cancer. This registry is a part of the Breast Cancer Family Registry (BCFR), an international resource of multi-generational families established for interdisciplinary collaborative research on breast cancer. The BCFR Cohort, established in 1995 at 6 sites is comprised of 34,000 individuals from 11,900 families who provided data on family history and epidemiologic risk factors as well as bio specimens. Over the next five years, the BCFR investigator team will continue 1) to actively follow the family cohort using common instruments and protocols, update the cancer family histories to identify new breast and other cancers in the families, and administer a follow-up questionnaire to update baseline epidemiologic data; 2) to maintain the extensive data and bio specimen resources and enhance them by conducting pathology review for all new breast cancers ascertained since baseline, completing molecular sub typing of tumors, and completing genotyping of known common breast cancer susceptibility variants; 3) to collect new data on screening, uptake of risk reductive and preventive health behaviors, knowledge of genetic disease, and uptake of genetic testing and communication to family members that will facilitate the translation of findings into clinical practice; and 4) to continue and expand collaborations with external investigators by sharing of BCFR data and bio specimen resources for a wide range of studies of gene discovery, cancer-related outcomes, risk factors in high-risk individuals, behavioral interventions and cancer prevention trials among at-risk family members. The BCFR Cohort is unique in that it is family-based and the first large prospective study of breast cancer risk for women at a continuum of risk. In addition to the unaffected cohort, the BCFR has one of the largest affected cohorts and will therefore provide a powerful resource for translational and clinical studies of recurrences, second primaries and survival.

www.metronyregistry.org
www.bcfamilyregistry.org

I have helped develop the biospecimen infrastructure of the above registry and the Long Island Breast Project which includes creating a bank of tissues and sections of tens of thousands of slides needed for research.
Service Activities

Hanina Hibshoosh earned his bachelor degree in chemistry and physics from NYU in 1981 and received the Brenner –Yeager Award for the outstanding student in physical chemistry at graduation. He earned an MD degree from New York Medical College in 1985. He did his residency in anatomic pathology at Columbia University (1985-89) and served as the chief resident in 1988-1989, and did post-doctoral work under Bernie Weinstein and Ricarrdo Dalla-Favera(1989-91). In 1991 he joined the staff of the department of Pathology at Columbia University as an assistant professor. He was the Director of the Breast Diagnostic Image Analysis Laboratory, of the Department of Pathology; College of Physicians and Surgeons, Columbia University, NY between 1993-2003. The laboratory was responsible for the characterization of all breast cancers for estrogen and progesterone receptor status, Her-2, proliferation marker Ki-67 and ploidy and s-phase analysis. He is currently a Professor of Pathology and Cell Biology at Columbia University Medical Center. He has extensive expertise and over 25 years of experience in diagnostic surgical pathology, especially in broad areas of cancer diagnostics and his special focus is on all aspects of breast diagnostics. His mentors included Karl Perzin and Raphael Lattes. He has given a weekly conference to the department of oncology entitled “Tumor board” for over 25 years covering all the solid tumor malignancies in the institution. Similarly he participates in a weekly conference entitled ”mammopath” discussing challenging breast pathology cases in a multi-disciplinary environment. He participates extensively in the departmental daily Quality assurance conference as well a semi-weekly surgical pathology teaching conference. He is involved with teaching of residents and fellows in both the department of pathology as well as oncology. He has taught/trained a generation of pathologists since 1989.

He has trained Breast Fellows who have assumed leading roles in a variety of academic setting including:

1) Dr. Bose- Director of Cytopathology-Cedars-Sinai/California
2) Dr. Gutierrez-Director of Breast Spore Pathology Core/National Tissue Resource-Baylor College of Medicine
3) Dr. Singh-Director of Breast Pathology NYU Medical center
4) Dr. Memeo-Head of Pathology, Mediterranean Institute of Oncology, Catania, Italy.
5) Manuelito Madrid, MD Breast Fellow Current Title: Breast Pathologist/Surgical Pathologist, Saint Luke’s Medical Center, Quezon City, Phillippines
6) Dr. Rojtman Chief of Clinical Microbiology, Meridian Health, N.J.
7) Dr. Ahmed Research Scientist, Molecular Pathology Core, Columbia University.

He taught medical and dental students pathology and in cancer biology course for graduate students.

He is highly accessible, characterized by a sign on his door that reads: “Don’t Ask, Don’t Knock, Just Walk In”!

Lastly, he has been the reference breast pathologist to the Breast Cancer Family Registry of New York since 1998.The Metropolitan New York Registry is a registry of families with a history of breast and/or ovarian cancer. The data and biospecimens donated by more than 8,000 high-risk families are being used by cancer researchers to identify new avenues for prevention, detection and treatment of breast cancer. With the help of thousands of families around the world - possibly including yours - the Registry is contributing to our growing understanding of breast cancer.

www.metronyregistry.org
www.bcfamilyregistry.org

Selected Publications

PTEN related articles (from discovery to characterization/the long and the short of it)

Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997 Mar 28;275(5308):1943-1947.

Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu JS, Malmström PO, Mansukhani M, Enoksson J, Hibshoosh H, Borg A, Parsons R. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res. 2005 Apr 1;65(7):2554-2559

Puc J, Keniry M, Li HS, Pandita TK, Choudhury AD, Memeo L, Mansukhani M, Murty VV, Gaciong Z, Meek SE, Piwnica-Worms H, Hibshoosh H, Parsons R. Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer Cell. 2005 Feb;7(2):193-204.

Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Maurer M, Koujak S, Ferrando AA, Malmström P, Memeo L, Isola J, Bendahl PO, Rosen N, Hibshoosh H, Ringnér M, Borg A, Parsons R. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7564-7569. Epub 2007 Apr 23.

Saal LH, Gruvberger-Saal SK, Persson C, Lövgren K, Jumppanen M, Staaf J, Jönsson G, Pires MM, Maurer M, Holm K, Koujak S, Subramaniyam S, Vallon-Christersson J, Olsson H, Su T, Memeo L, Ludwig T, Ethier SP, Krogh M, Szabolcs M, Murty VV, Isola J, Hibshoosh H, Parsons R, Borg A. Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet. 2007 Dec 9;

3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma. Maurer M, Su T, Saal LH, Koujak S, Hopkins BD, Barkley CR, Wu J, Nandula S, Dutta B, Xie Y, Chin YR, Kim DI, Ferris JS, Gruvberger-Saal SK, Laakso M, Wang X, Memeo L, Rojtman A, Matos T, Yu JS, Cordon-Cardo C, Isola J, Terry MB, Toker A, Mills GB, Zhao JJ, Murty VV, Hibshoosh H, Parsons R. Cancer Res. 2009 Aug 1;69(15):6299-306. Epub 2009 Jul 14.

Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a. Fine B, Hodakoski C, Koujak S, Su T, Saal LH, Maurer M, Hopkins B, Keniry M, Sulis ML, Mense S, Hibshoosh H, Parsons R. Science. 2009 Sep 4;325(5945):1261-5.

A Secreted PTEN Phosphatase that Enters Cells to Alter Signaling and Survival.Hopkins BD, Fine B, Steinbach N, Dendy M, Rapp Z, Shaw J, Pappas K, Yu JS, Hodakoski C, Mense S, Klein J, Pegno S, Sulis ML, Goldstein H, Amendolara B, Lei L, Maurer M, Bruce J, Canoll P, Hibshoosh H, Parsons R. Science. 2013 Jun 6.

Autophagy/(Beclin 1 initial characterization as the first mammalian gene associated with autophagy)

Liang XH., Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B, Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999 Dec 9;402,(6762); 672-676.

Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, Rosen J, Eskelinen EL, Mizushima N, Ohsumi Y, Cattoretti G, Levine B. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest. 2003 Dec;112(12):1809-1820. Epub 2003 Nov 24

Oncogenes/tumor suppressor genes discovery/characterization

Xia W, Nagase S, Montia AG, Kalachikov SM, Keniry M, Su T, Memeo L, Hibshoosh H, Parsons R.BAF180 is a critical regulator of p21 induction and a tumor suppressor mutated in breast cancer. Cancer Res. 2008 Mar 15;68(6):1667-74.

Sagiv E, Memeo L, Karin A, Kazanov D, Jacob-Hirsch J, Mansukhani M, Rechavi G, Hibshoosh H, Arber N. CD24 is a new oncogene, early at the multistep process of colorectal cancer carcinogenesis. Gastroenterology. 2006 Aug;131(2):630-639.

Yu JS, Koujak S, Nagase S, Li CM, Su T, Wang X, Keniry M, Memeo L, Rojtman A, Mansukhani M, Hibshoosh H, Tycko B, Parsons R. PCDH8, the human homolog of PAPC, is a candidate tumor suppressor of breast cancer. Oncogene. 2008 Aug 7;27(34):4657-65.

Klinakis A, Szabolcs M, Chen G, Xuan S, Hibshoosh H, Efstratiadis. Igf1r as a therapeutic target in a mouse model of basal-like breast cancer. A. Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2359-64.):4657-65

Yao Y, Slosberg ED, Wang L, Hibshoosh H, Zhang YJ, Xing WQ, Santella RM, Weinstein IB Increased susceptibility to carcinogen- induced mammary tumors in MMTV-Cdc25B Transgenic Mice. Oncogene, 1999 Sep 16;18(37): 5159-5166

Li CM, Margolin AA, Salas M, Memeo L, Mansukhani M, Hibshoosh H, Szabolcs M, Klinakis A, Tycko B. PEG10 is a c-MYC target gene in cancer cells. Cancer Res. 2006 Jan 15;66(2):665-672.

Hibshoosh H, Johnson M, Weinstein IB. Effects of overexpression of ornithine decarboxylase (ODC) on growth control and oncogene-induced cell transformation. Oncogene. 1991 May;6(5):739-743.

Arber N., H Hibshoosh, Moss SF, Sutter T., Zhang Y., Begg M., Wang S., Weinstein IB, Holt PR Increased expression of Cyclin D1 is an early event in multistage Colorectal carcinogenesis. Gastroenterology 1996; Mar; 110(3):669-674.

Iida S, Rao PH, Nallasivam P, Hibshoosh H, Butler M, Louie DC, Dyomin V, Ohno H, Chaganti RS and Dalla-Favera R. The t(9;14)(p13:q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 Gene. Blood 1996 Dec 1;88(11):4110-4117 (on cover).

Molecular Epidemiology

Gammon MD, Hibshoosh H, Terry MB, Bose S, Schoenberg JB, Brinton LA, Bernstein JL, Thompson WD. Cigarette smoking and other risk factors in relation to p53 expression in breast cancer among young women. Cancer Epidemiol Biomarkers Prev. 1999 Mar;8(3):255-263.

Gammon MD, Hibshoosh H, Terry MB, Bose S, Schoenberg JB, Brinton LA, Bernstein JL, Thompson WD. Oral contraceptive use and other risk factors in relation to HER-2/neu overexpression in breast cancer among young women. Cancer Epidemiol Biomarkers Prev. 1999 May;8(5):413-419.

Terry MB, Gammon MD, Schoenberg JB, Brinton LA, Arber N, H Hibshoosh Oral contraceptive use and Cyclin D1 overexpression in breast cancer among young women. Cancer Epidemiology, Biomarkers and Prevention 2002 Oct; 11(10 Pt 1):1100-1103.

Terry MB, Neugut AI, Mansukhani M, Waye J, Harpaz N, Hibshoosh H. Tobacco, alcohol, and p53 overexpression in early colorectal neoplasia. BMC Cancer. 2003 Nov 6;3:29.
Gammon MD, Terry MB, Arber N, Chow WH, Risch HA, Vaughan TL, Schoenberg JB, Mayne ST, Stanford JL, Dubrow R, Rotterdam H, West AB, Fraumeni JF Jr, Weinstein IB, Hibshoosh H. Nonsteroidal anti-inflammatory drug use associated with reduced incidence of adenocarcinomas of the esophagus and gastric cardia that overexpress cyclin D1: a population-based study. Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):34-39.

Joe AK, Memeo L, Mckoy J, Mansukhani M, Liu H, Avila-Bront A, Romero J, Li H, Troxel A, Hibshoosh H. Cyclin D1 overexpression is associated with estrogen receptor expression in Caucasian but not African-American breast cancer. Anticancer Res. 2005 Jan-Feb;25(1A):273-281

Bane AL, Beck JC, Bleiweiss I, Buys SS, Catalano E, Daly MB, Giles G, Godwin AK, Hibshoosh H, Hopper JL, John EM, Layfield L, Longacre T, Miron A, Senie R, Southey MC, West DW, Whittemore AS, Wu H, Andrulis IL, O'Malley FP. BRCA2 mutation-associated breast cancers exhibit a distinguishing phenotype based on morphology and molecular profiles from tissue microarrays. Am J Surg Pathol. 2007 Jan;31(1):121-128.

Risk factors for uncommon histologic subtypes of breast cancer using centralized pathology review in the Breast Cancer Family Registry. Work ME, Andrulis IL, John EM, Hopper JL, Liao Y, Zhang FF, Knight JA, West DW, Milne RL, Giles GG, Longacre TA, O'Malley F, Mulligan AM, Southey MC, Hibshoosh H, Terry MB. Breast Cancer Res Treat. 2012 Aug;134(3):1209-20. doi: 10.1007/s10549-012-2056-y. Epub 2012 Apr 25.

Carcinogenesis/miscellaneous

Hibshoosh H, Lattes R. Immunohistochemical and molecular genetic approaches to soft tissue tumor diagnosis: a primer. Semin Oncol. 1997 Oct;24(5):515-525. Review.

Geacintov NE, Hibshoosh H, Ibanez V, Benjamin MJ, Harvey RG.; Mechanisms of reaction of benzo(a)pyrene-7,8-diol-9,10-epoxide with DNA in aqueous solutions, Biophys Chem. 1984 Aug;20(1-2):121-133.

Arber N, Hibshoosh H, Yasui W, Neugot AI, Hibshoosh A, Yao Y, Sgambato A, Yamamoto H, Shapira I, Rosenman D, Fabian I, Weinstein IB, Tahara E, Holt PR.Abnormalities in the expression of cell cycle-related proteins in tumors of the small bowel. Cancer Epidemiol Biomarkers Prev, 1999 Dec;8(12):1101-1105.

Sgambato A, Zhang YJ, Arber N, Hibshoosh H, Doki Y, Ciaparrone M, Santella RM, Cittadini A, Weinstein IB. Deregulated expression of p27(Kip1) in human breast cancers. Clin Cancer Res. 1997 Oct;3(10):1879-1887.

Oken SM, Mercado CL, Memeo L, Hibshoosh H. Invasive ductal carcinoma with fibrotic focus: mammographic and sonographic findings with histopathologic correlation. AJR Am J Roentgenol. 2005 Aug;185(2):490-494.

Committees , Council, and Professional Society Memberships

NASABP-pathology coordinator at CPMC

1987-1989-Representative of the Department of Pathology House Staff Affairs Committee.

1991- Elected Member of the Faculty Council of the Faculty of Medicine

1992- Member of the Cancer committee of CPMC

1993-Member Department of Pathology IRB Committee

1994-1996-1998 Elected and re-elected member of the Executive Committee of the Faculty of Medicine

1994-Member Breast Cancer Executive Committee

1995-Member Cancer Registry Oversight Committee

1997-Member Liaison Committee of Department of Pathology/Surgery

2000-Member New-York Presbyterian Hospital Oncology Service line Executive Council


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