Biography: 

Prior to joining the Arizona Cancer Center and the University of Arizona College of Medicine, Dr. Ablin served consecutively as Director, Scientific Investigation at Tetragenex Pharmaceuticals, Inc. (Park Ridge, NJ), and Director, Immunobiology Unit, Department of Urology and Research Associate Professor of Urology, State University of New York at Stony Brook School of Medicine. He is President of the Robert Benjamin Ablin Foundation for Cancer Research, founded in memory of his father, since 1979. Dr. Ablin received his Ph.D. in Microbiology from the State University of New York at Buffalo in 1967, following which he continued his training in immunology as a United States Public Health Service Postdoctoral Fellow at the Medical School under the late renowned Distinguished Professor Ernest Witebsky. Dr. Ablin recently received the degree of D.Sc., honoris causa, from Lake Forest College, his undergraduate alma mater.

Dr. Ablin discovered prostate-specific antigen (PSA) in 1970, for which he was a nominee for the Lasker Award in 1997. His discovery of PSA led to the development of the PSA test. A pioneer of cryosurgery and the concept of “cryoimmunotherapy” for the treatment of cancer, Dr. Ablin has extensive experience in cancer research, particularly in the study of the development and metastasis of cancer. A member of Phi Beta Kappa and various professional societies, including the American Association for Cancer Research, the American Association of Immunologists, the British Association of Surgical Oncology, the New York Academy of Sciences, and Sigma Xi, he was a founding member and Vice President (1977-80) of the American College of Cryosurgery and served as President (1977-80) of the International Society of Cryosurgery, who named him Honorary Life-Time President in 1980. Dr. Ablin is a Diplomat of the American Board of Clinical Immunology and Allergy and certified by the American Academy of Microbiology in Public Health and Medical Laboratory Microbiology. Cited in several biographical references, including American Men and Women of Science, Who's Who of Emerging Leaders in America and Who's Who in the World, he has been an invited speaker at numerous national and international scientific meetings and has contributed numerous articles to professional journals and texts. Dr. Ablin is co-editor of the book series Cancer Metastasis - Biology and Treatment and serves on the editorial board of several journals, including Clinical and Diagnostic Laboratory Immunology , Current Opinion in Oncology , Experimental Biology and Medicine , International Journal of Oncology and UroOncology .

Summary of Research Activity:

Studies are directed toward: a) ascertaining the role of the inter- and/or intratumoural microenvironment (milieu) in contributing to the development and progression of cancer; b) the differentiation of latent (indolent) cancer from one that is aggrressive and clinically important and should be treated and c) development of response criteria (biological markers) to evaluate the effectiveness of new therapeutic regimens and/or agents for cancer.

Selected Publications: 

• Ablin RJ. An appreciation and realization of the concept of cryoimmunology, p.136.  In Onik GM, Rubinsky B, Watson G and Ablin RJ. (Eds.): Percutaneous Prostate Cryoablation. Quality Medical Publishing, Inc., St. Louis, 1995.
• Ablin RJ. A retrospective and prospective overview of prostate-specific antigen. J. Cancer Res. Clin. Oncol.,  123 :583, 1997.
• Zaviacic M and Ablin RJ. The female prostate and prostate-specific antigen.  Immunohistochemical localization, implications of this prostate marker in women and reasons for using the term "prostate" in the human female.  Histol. Histopathol., 15 :131, 2000.
• Jiang WG, Ablin RJ, Douglas-Jones A and Mansel RE. Expression of transglutaminases in human breast cancer and their possible clinical significance. Oncol. Rep., 10 :2039, 2003.
• Szabo KA, Ablin RJ and Singh G. Matrix metalloproteinases and the immune response. Clin. Appl. Immunol. Rev., 4 :295, 2004.

Collaborative Research: 

• Wen G. Jiang, M.B., B.Ch., M.D., Metastasis & Angiogenesis Research Group, Department of Surgery, Wales College of Medicine, Cardiff University, Cardiff, United Kingdom: Role of select macromolecules in breast and prostate cancer.
• Mukta M. Webber, Ph.D., Departments of Zoology and Medicine, Michigan State University, East Lansing, Michigan: Chemoprevention and treatment of prostate cancer.
• Milan Zaviacic, M.D., Ph.D., D.Sc., Institute of Pathology, Comenius University School of Medicine, Bratislava, Slovakia: Human female prostate.

Biography: 

Summary of Research Activity:

Mechanism of Antigenic Variation in Giardia lamblia and control of VSP expression - G. lamblia trophozoites undergo antigenic variation of a major surface antigen (VSPs). This antigenic variation may explain the chronicity of Giardia infections as well as the ability of trophozoites to infect the intestines of multiple different mammals. The focus of my laboratory has been to determine the molecular mechanism by which antigenic variation occurs and how VSP expression is controlled.

The Genetics of Giardia lamblia - Giardia trophozoites are fairly unique in their possession of two nuclei, which are equivalent by all criteria that have been examined to date. Current evidence from my laboratory and others suggests that the trophozoites are tetraploid, each made up of two diploid nuclei, and that they reproduce asexually. We have developed a DNA:DNA fluorescence in situ hybridization (FISH) to examine similarities and differences between the nuclei.

Giardia genome project - As part of a multi-center project funded by the NIH, we are determining the sequence of the Giardia genome. Our work has included analysis of the vsp genes, RNA polymerase genes, and the histone modification enzymes (acetylase, deacetylase, methylase, and kinase). This work will also help us to develop a better molecular classification system for Giardia.

Mechanism of Antigenic Variation in Giardia lamblia and control of VSP expression - G. lamblia trophozoites undergo antigenic variation of a major surface antigen (VSPs). This antigenic variation may explain the chronicity of Giardia infections as well as the ability of trophozoites to infect the intestines of multiple different mammals. The focus of my laboratory has been to determine the molecular mechanism by which antigenic variation occurs and how VSP expression is controlled.

The Genetics of Giardia lamblia - Giardia trophozoites are fairly unique in their possession of two nuclei, which are equivalent by all criteria that have been examined to date. Current evidence from my laboratory and others suggests that the trophozoites are tetraploid, each made up of two diploid nuclei, and that they reproduce asexually. We have developed a DNA:DNA fluorescence in situ hybridization (FISH) to examine similarities and differences between the nuclei.

Giardia genome project - As part of a multi-center project funded by the NIH, we are determining the sequence of the Giardia genome. Our work has included analysis of the vsp genes, RNA polymerase genes, and the histone modification enzymes (acetylase, deacetylase, methylase, and kinase). This work will also help us to develop a better molecular classification system for Giardia.

Selected Publications: 

• Adam, R., Hunter, G., DiTomasso, J., Comerci, Jr., G. Mucormycosis: Emerging Prominence of Cutaneous Infections. Clinical Infectious Diseases 19:67-76, 1994.

• Strasser, M.D., Kennedy, R.J., Adam, R.D. Rhinocerebral Mucormycosis with Cavernous Sinus Involvement: Successful Medical Therapy with Amphotericin B Lipid Complex. Arch. Intern. Med, 156:337-339, 1996.

• Adam, R.D. The Biology of Giardia lamblia. Clinical Microbiology Reviews, 14:447-475, 2001.

• Yu, L., C.W. Birky, Jr., and R.D. Adam. The Two Nuclei of Giardia each have Complete Copies of the Genome and are Partitioned Equationally at Cytokinesis, in press, Eukaryotic Cell.

• Seshadri, V., A.G. McArthur, H.G. Morrison, M.L. Sogin, and R.D. Adam. Giardia lamblia RNA polymerase II: Amanitin-Resistant Transcription, in preparation.

Collaborative Research: 

Biography: 

B.A .: University of Dublin , Trinity College , Dublin , Ireland 1978
Ph.D. : University of Michigan , Ann Arbor , MI 1984
Postdoctoral : University of Edinburgh , Edinburgh , Scotland 1985
Massachusetts Institute of Technology, Cambridge , MA 1986-88
Genentech, Incorporated, South San Francisco , CA 1988-90

Faculty Positions:

1990-96 Assistant Professor,Department of Molecular and Cellular Biology,University of Arizona , Tucson , AZ.

1996-8/01 Associate Professor,Department of Molecular and Cellular Biology, University of Arizona , Tucson , AZ

10/00-7/02 Lecturer School of Biological Sciences University of Sussex , UK

1/03-5/04 Associate Lecturer,Chichester College and University College , Chichester W. Sussex, UK

8/04- Assistant Professor, Northern Arizona University Flagstaff , AZ

Summary of Research Activity:

The overall goal of our work is to understand how environmental exposure and genetic factors influence the risk of genomic instability in cancer. During cancer development, chromosomes undergo breakages that lead to rearrangements, which are often unstable and consequently result in further breakage and rearrangements. Such events lead to translocations, deletions, inversions etc, and may result in altered gene products and/or changes in gene expression. This, in turn, can affect growth control, and consequently lead to cancer.

The mechanisms by which these events occur are not well understood. We are particularly interested in events that occur at specific sites in the genome. Dr. Ted Weinert's lab at the University of Arizona has established a system for studying events that occur at particular sites in chromosomes of yeast. His lab is studying what features make such sites particularly susceptible to instability. In collaboration with his lab, we are using this system to learn (i) what gene products are important in stabilizing the genome, and (ii) what environmental factors may influence instability. Several gene products are already known from work in the Weinert lab – for example, some of the check-point genes, as well as some of the genes involved in DNA replication. We are using a genetic screen to identify additional genes that, when either mutant or overexpressed, increase genomic instability. These genes will then be analyzed to identify gene products that are normally required to help stabilize the genome. Ultimately, we plan to extend these observations to human cells by determining whether human orthologs of genes identified in yeast cause DNA rearrangements in human cells that are relevant to cancer.

To address the role of environmental factors in genomic instability, we are first asking whether uranium and arsenic increase the levels of instability in yeast. We are particularly interested in arsenic and uranium as, on the Navajo reservation near Northern Arizona University , these are present at elevated levels in the well-water. An abnormally high incidence of various cancers has been reported on the reservation, and it has been suggested that this may be at least partly due to the high levels of arsenic and uranium. We are examining the effects of arsenic and uranium, either alone or in combination, on genomic instability in yeast. In addition, we are testing whether synergisitc effects are seen when arsenic, uranium or both are combined with mutant or overexpressed genes that affect genomic instability. Eventually, we plan to extend these studies to human cells.

Selected Publications: 

Adams , A.E.M. , D. Botstein, and D.G. Drubin. 1989. A yeast actin-binding protein is encoded by SAC6, a gene found by suppression of an actin mutation. Science 243: 231-233.

Adams , A.E.M. , D. Botstein, and D.G. Drubin. 1991. Yeast fimbrin is required in vivo for actin organization and morphogenesis. Nature 354: 404-408.

Honts, J.E., T.S. Sandrock, S.M. Brower, J.L. O'Dell, and A.E.M. Adams . 1994. Actin mutations that show suppression with fimbrin mutations identify a likely fimbrin-binding site on actin. J. Cell Biol. 126:413-422.

Brower, S.M., J.E. Honts, and A.E.M. Adams . 1995. Genetic analysis of the fimbrin-actin binding interaction in Saccharomyces cerevisiae. Genetics 140:91-101.

Sandrock, T.M., J.L. O'Dell, and A.E.M. Adams . 1997. Allele-specific suppression by formation of new protein-protein interactions. Genetics . 147:1635-42.

Sandrock., T.M., S.M. Brower, K.A. Toenjes, and A.E.M. Adams . 1999. Suppressor analysis of fimbrin (Sac6p) overexpression in yeast . Genetics 151: 1287-97.

Whitacre, J.L., D. A. Davis, K.A. Toenjes, S.M. Brower, and A.E.M. Adams . 2001. Generation of an isogenic collection of yeast actin mutants and identification of three interrelated phenotypes. Genetics . 157(2):533-43.

Kandl, K.A., R. Munshi, Ortiz P.A., Andersen, G.R., Kinzy, T.G., and A.E.M. Adams 2002. Identification of a role for actin in translational fidelity in yeast. Molecular Genet. Genomics. 268 (1) 10-18

Collaborative Research: 

Weinert, T.A. AZCC. Using yeast to understand genomic instability in cancer

Dixon , K. UA. Extending studies of yeast genes involved in genomic instability to studies of their orthologs in mammalian cells.

Biography: 

Summary of Research Activity:

Pediatric AIDS is one of the fastest growing aspects of the AIDS pandemic in the United States and worldwide, as a greater number of women in the childbearing age group are infected with HIV-1. Infants born to mothers infected with HIV-1 are at risk of acquiring HIV-1 infection and subsequently developing AIDS. The World Health Organization (WHO) estimates that by the year 2000, 10 million children will have been born HIV infected.

Mother-to-infant transmission of HIV-1 mainly occurs perinatally at an estimated rate of more than 30 percent. In addition, AIDS-related or unrelated cancers can influence HIV-1 transmission and infection in mothers and infants. However, the molecular mechanisms of maternal transmission of HIV-1 are not known, which makes it difficult to define strategies for prevention and treatment of HIV-1 infection in children.

Genetic studies from my laboratory suggested that a minor subtype of maternal virus from the genetically heterogeneous virus population was transmitted to the infant. The minor HIV-1 genotype predominates initially as a homogeneous population in the infant and then becomes diverse as the infant grows older. Moreover, we don't understand the molecular and biological properties of the HIV-1 that is transmitted from mother to infant.

Our hypothesis is that specific molecular and biological properties of HIV-1 are critical determinants of perinatal transmission. A better characterized HIV-1 transmitted from mother to infant will contribute to the understanding of the molecular mechanisms involved in maternal transmission of HIV-1. Furthermore, the elucidation of the viral determinants involved in maternal transmission may allow AIDS researchers to develop methods to prevent mother-to-infant transmission by means of perinatal interventions, such as gene therapy, immunotherapy, antiviral therapy, and a preventive vaccine.

Selected Publications: 

• Ahmad N, Baroudy BM, Baker RC, Chappey C. Genetic analysis of human immunodeficiency virus type 1 envelope V3 region isolates from mothers and infants after perinatal transmission. J Virol 69:1001-1012, 1995.

• Yedavalli VRK, Chappey C, Matala E, Ahmand N. Conservation of an intact vif gene of human immunodeficiency virus type 1 during maternal-fetal transmission. J Virol 72:1092-1102, 1998.

• Yedavalli VRK, Chappey C, and Ahmad N. Maintenance of an intact human immunodeficiency virus type 1 vpr gene following mother-to-infant transmission. J Virol 72:6937-6943, 1998.

Collaborative Research: 

• Ziad M. Shehab, M.D., Department of Pediatrics, College of Medicine.

• Dominick DeLuca, Ph.D., Department of Microbiology and Immunology, College of Medicine.

• Neil Ampel, M.D., Department of Medicine and V.A. Medical Center, Tucson, Arizona.

• Colombe Chappey, Ph.D., NCBI, NLM, National Institutes of Health, Bethesda, Maryland.

Biography: 

Summary of Research Activity:

In collaboration with other faculty members in the Prostate Cancer Research Group, I have been conducting clinically based integrative research in men afflicted with prostate cancer since the early 1980s. My main areas of current interest and of previous accomplishments include the following:

• Studies into using serum PSA levels for the case finding and screening for prostate cancer.
• Studies of the characteristics and clinical correlations of several serum PSA assays.
• Phase I, II, and III studies of sustained release LHRH agonists and the anti-androgen bicalutamide.
• Neoadjuvant and adjuvant approaches for prostate cancer primary therapy.
• Prostate cancer prevention trials.
• Phase I, II, and III studies of new therapies for hormone refractory prostate cancer.
• Studies into the effectiveness of palliative interventions in prostate cancer.
• New approaches in men with micrometastatic prostate cancer.

Selected Publications: 

• Ahmann FR, Citrin DL, DeHaan HA, Guinan P, Jordan VC, Kreis W, Scott M, Trump DL. Zoladex: a sustained release monthly LHRH analogue for the treatment of advanced prostate cancer. JCO 5:912-917, 1987.
• Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, Flanigan RC, DeKernion JB, Ratliff TL, Kavoussi LR, Dalkin BL, Waters WB, MacFarlane MT, Southwick PC. Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multi-center clinical trial of 6,630 men. J of Urology 151:1283-1290, 1994.
• Dalkin BL, Ahmann FR, Nagle R, Johnson CS. Randomized study of neoadjuvant testicular androgen ablation therapy before radical prostatectomy in men with clinically localized prostate cancer. J of Urology 155:1357-1360, 1996.

Collaborative Research: 

• Bruce Dalkin, M.D., Associate Professor of Surgery, Chief, Division of Urology.
• Ray Nagle, M.D., Ph.D., Professor of Pathology, Chief, Immunopathology.
• Evan Hersh, M.D., Professor of Medicine, Chief of Immunobiologic Research.

Biography: 

Summary of Research Activity:

After training at the NCI serving on the faculty and at the University of California, San Francisco, he moved in 1975 from UCSF to the University of Arizona Cancer Center, where he served as Director of the Cancer Prevention and Control Program from 1989 to 2005. The hallmark of his research career has been to take promising anticancer and chemopreventive agents, such as a -difluoromethylornithine (DFMO), ursodeoxycholic acid, selenium and sulindac sulfone from basic studies of their pharmacology all the way to the clinic. He has been continuously funded as PI of Program Project grants in colon (CCPPP) and skin cancer prevention since the 1980's. Four areas of his research are:

1. Retinoids in cancer treatment and prevention. Dr. Alberts' group has conducted landmark basic and clinical studies of retinoids (References #'s 65, 79, 94, 124, 129, 130, 163, 168). In a 2,297 patient trial (# 293), they reported that retinol is effective in preventing squamous cell skin cancer. Dr. Alberts helped demonstrate that topically applied all-trans-retinoic acid leads to regression of cervical intraepithelial neoplasia III (moderate dysplasia) (#'s 84, 135, 242). In a recent dose-finding trial of oral Vitamin A in participants with sun-damaged skin, he reported both efficacy and mechanism of action (# 399).

2. Biomarkers of skin carcinogenesis. Dr. Alberts helped to develop a panel of biomarkers for skin carcinogenesis, including proliferating cell nuclear antigen (PCNA), p53, polyamine levels and apoptosis (#'s 290, 324, 359). The biomarkers have been key to subsequent therapeutic trials, such as the demonstration that topical DFMO can prevent formation of actinic keratoses and reverse sun-related DNA damage (# 340). Dr. Alberts' group has developed topically administered chemopreventive agents that can be incorporated into sunscreens (#s 340, 362, 370). In a recent collaboration with Dr. Jeffrey Trent and others, reported in Nature (# 334), gene expression profiles were used develop a novel and clinically relevant taxonomy of malignant melanomas. Dr. Alberts' group has established VEGFR expression in pigmented moles as a biomarker that can differentiate dysplastic from benign nevi (# 434).

3. Prevention of colon cancer. Dr. Alberts has been a pioneer in the use of adenoma recurrence as a surrogate endpoint for preventing colon cancer in large population-based studies. Phase I and II studies of wheat bran fiber (WBF) preceded his negative phase III randomized study of WBF dietary supplementation (#'s 190, 184, 254, 261, 267, 271, 285, 287). The final results of a phase III randomized study of ursodeoxycholic acid (UDCA) for preventing adenoma recurrence in 1,285 randomized participants followed for three years after initial polypectomy revealed a 39% reduction in the recurrence of highly dysplastic polyps (i.e., the ones most likely to advance to invasive colorectal cancers) (#s 301, 420). The rationale for this study came partly from a phase I study demonstrating that UDCA could “washout” deoxycholic acid in fecal water (# 402). Enrollment began in 2002 for a phase III study of celecoxib and selenium, individually and together, to prevent adenoma recurrence in 1,600 patients. Previously, Dr. Alberts helped to oversee the Arizona Cancer Center phase III trial of selenium in 1,302 resected non-melanoma skin cancer patients. A secondary analysis of this trial documented a selenium-associated 56% reduction in risk of colon cancer incidence and a nearly 70% reduction in prostate cancer risk, which led to the 32,000 male SELECT phase III trial (# 278).

In another secondary analysis, a higher intake of Ca 2+ reduced by 45% the rate of adenoma recurrence in the WBF study (# 360). High-dose WBF supplementation failed to reduce secondary bile acid levels in fecal water in patients with resected colon adenomas; this finding may underlie the relative inactivity of WBF as a polyp prevention agent (# 372). A secondary analysis of the WBF trial data in combination with the NCI's high fiber vegetables and fruit phase III polyp prevention trial suggests that male polyp patients (but not female) may benefit from a high fiber diet to prevent polyp recurrence (# 5). Clinically vital new information concerning characteristics of incident adenomas that predict recurrence was also reported ( #s 318, 346).

4. Nuclear karyometric analysis as a biomarker of early neoplasia. In a series of recent papers published in collaboration with Dr. Peter Bartels in the Optical Science Center at the University of Arizona, Dr. Alberts has reported that subtle karyometric features of nuclear chromatin texture and spatial distribution denote very early neoplastic changes in skin, endometrium, ovary, cervix, colon, bladder and breast (#s 299, 352, 344, 347, 392, 357, 364, 380, 392, 393, 398, 408, 410, 421, 425). These statistically significant findings are of potentially great importance because they arise when the early neoplastic and normal cells are otherwise completely indistinguishable by all conventional histological criteria. The nuclear karyometric approach is beginning to have a major impact on identification of individuals at high risk for cancer and as a sensitive biomarker of response to chemopreventive agents (#s 393, 398).

Dr. Alberts has served as the Principal Investigator on NCI's phase I contracts for chemopreventive agent phase I/II clinical trials since the Task Orders were first competed in the early 1990s. His research group, headed by Dr. Sherry Chow, Associate Professor of Pharmacy, was recently awarded a five-year Phase I/II Chemopreventive Agent Consortium agreement worth $7.5 million. He has been the principal investigator on both T32 and R25T Cancer Prevention and Control Training Grants (2002-2010) and has served as a thesis advisor for more than 15 doctoral degree candidates and a major mentor for 17 post-doctoral fellows, including Drs. Gary Goodman (Chair of the Chemoprevention Subcommittee in the Southwest Oncology Group), Scott Lippman (Chair, Department of Thoracic and Head and Neck Cancer, University of Texas – M.D. Anderson Cancer Center), Dr. William Dalton (Director, Lee Moffitt Cancer Center, Tampa) and Dr. Robert T. Dorr (Director of the Developmental Therapeutics Program, Arizona Cancer Center).

Dr. Alberts has made numerous contributions beyond his own research to advancing the cause of cancer prevention. He has served as the Chair of the FDA's Oncologic Drug Advisory Committee (1982-1984), was a member of the NCI's Board of Scientific Advisors (1997-2006), is Co-Editor-in-Chief of Cancer Epidemiology, Biomarkers and Prevention (2002-2007), and Chairs the Cancer Prevention and Control Committee in the Gynecologic Oncology Group (1995-present). He received the American Society of Clinical Oncology ACS Cancer Prevention Award in 1999, the American Association for Cancer Research Joseph Burchenal Eighth Annual Award for Excellence in Clinical Research in 2003 and the American Society of Preventive Oncology Distinguished Career Award in 2003. In 2004, Dr. Alberts received the third annual AACR-Cancer Research and Prevention Foundation Award for Excellence in Cancer Prevention Research which is given annually to a scientist residing in any country in the world for his or her seminal contributions to the field of cancer prevention. Research must have had not only a major impact on the field, but must also have stimulated new directions in this important area. In conclusion, Dr. David Alberts is without question one of the world leaders in the field of cancer prevention research.

Selected Publications: 

Bartels PH, Ranger-Moore J, Stratton MS, Bozzo, P, Einspahr J, Liu Y, Thompson D, Alberts DS: Statistical analysis of chemopreventive efficacy of vitamin A in sun-exposed, normal skin. Analyt Quant Cytol Histol 24:185-197, 2002.
Alberts DS, Dorr RT, Einspahr JG, Aickin M, Saboda K, Xu MJ, Peng YM, Goldman R, Foote JA, Warneke JA, Salasche S, Roe DJ, Bowden GT: Chemoprevention of human actinic keratoses by topical 2-(difuoromethyl-dl-ornithine. Cancer Epidemiol Biomarkers Prev 9:1281-1286, 2000.
Alberts DS, Martínez E, Roe D, Guillen-Rodriguez MS, Marshall J, van Leeuwen B, Reid M, Ritenbaugh C, Vargas P, Bhattacharyya AB, Earnest D, Sampliner R, and the Phoenix Colon Cancer Prevention Physicians' Network. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. NEJM, Vol. 342:1156-1162, April 20, 2000.

Collaborative Research: 

Peter Bartels, Ph.D., Optical Sciences: nuclear chromatin texture analysis of precancerous lesions in the breast, colon, endometrium, ovary, prostate and skin.
Janine G. Einspahr, Ph.D.: immunohistochemical biomarkers in colon, breast, endometrium, cervix, and prostate intraepithelial neoplasias and cancers.
G. Timothy Bowden, Ph.D., Radiation Oncology: UV carcinogenesis in animals and humans.
Eugene Gerner, Ph.D., Radiation Oncology: colon carcinogenesis and chemoprevention in animal models.
Robert T. Dorr, Ph.D., Department of Pharmacology: development of topical chemoprevention agents.
Jeffrey Trent, Ph.D., President of T-GEN (Translational Genomics Research Institute), Phoenix: chemopreventive agents that hit specific molecular targets in non-melanoma and melanoma skin cancers.
Dennis Ahnen, M.D., University of Colorado Cancer Center: molecular colon carcinogenesis.
Stanley Hamilton, M.D., University of Texas, M.D. Anderson Cancer Center: molecular colon carcinogenesis.
Jean Pierre Issa, Ph.D., University of Texas, M.D. Anderson Cancer Center: gene methylation in colon adenomas and cancers and colonic mucosa.
Gerald Salen, Ph.D., University of New Jersey Medical and Dental School: fecal bile acids and colon carcinogenesis.
Xiao Xu, Ph.D., University of Texas, M.D. Anderson Cancer Center: retinoid receptors in human skin.
Steven P. Stratton, Ph.D., Department of Medicine: phase I studies of chemopreventive agents.
Sherry Chow, Ph.D.: phase I and II studies of chemopreventive agents
Zigang Dong, Ph.D., Hormel Institute, University of Minnesota: mechanisms of UVA-induced skin cancer in mice and humans.

Biography: 

Summary of Research Activity:

Selected Publications: 

Collaborative Research: 

Biography: 

Summary of Research Activity:

Selected Publications: 

Collaborative Research: 

Biography: 
Terry Badger has worked at the University of Arizona College of Nursing since 1986. She came to UA after completing her PhD from The University of Texas, Austin.   Her research interests focus on psychosocial issues in cancer. She is currently testing a telephone counseling intervention with women with breast cancer and their partners.

Summary of Research Activity:

Ongoing Research Support

Badger (PI)                                                                     2003-2005
NINR, NIH
1 R15NR008001-01A1
Telephone Intervention:  Rural Women w/Cancer & Partners
The purpose of this study is to test the effectiveness of the telephone interpersonal counseling intervention
compared to an exercise intervention and control group on symptom management (depressive symptoms and fatigue) and quality of life in rural women with breast cancer and their partners

Selected Publications: 

Badger, T.A., Segrin, C., Meek, P., Lopez, A.M. & Bonham, E.  (2004).  Responders and nonresponders to a telephone interpersonal counseling intervention in women with breast cancer.  Journal of Psychosocial Oncology, 13 (supplemental), S40 .

Badger, T.A., Segrin, C., Meek, P., Lopez, A.M. & Bonham, E.  (2004).  A case study of telephone interpersonal counseling with a woman with breast cancer and her partner. Journal of Psychosocial Oncology, 13 (supplemental), S59-60 .

Badger, T.A., Segrin, C., Meek, P., Lopez, A.M., & Bonham, C. (i2004). A case study of telephone interpersonal counseling with women with breast cancer and their partners.  Oncology Nursing Forum, 31 (5), 997-1003.

Badger, T.A., Gelenberg, A., & Berren, M. (2004).  Consultative intervention to improve outcomes of high utilizers in a public mental health system. Perspectives of Psychiatric Care, 40, 53-69.

Badger, T.A., Segrin, C., Meek, P., Lopez, A.M., Bonham, E. & Sieger, A.  (2005). Telephone interpersonal counseling with women with breast cancer: Symptom management and quality of life.  Oncology Nursing Forum, 32 (2), 273-279.

Bennett, G. & Badger, T.A. (2005).  Depression in men with prostate cancer: A Review. Oncology Nursing Forum, 32 (3), 545-556.

Badger, T.A., Segrin, C., Meek, P., Lopez, A.M., & Bonham, E. (in press)  Profiles of women with breast cancer: Who responds to a telephone interpersonal counseling intervention? Journal of Psychosocial Oncology.

Segrin, C., Badger, T.A., Meek, P., Sieger, A.  & Lopez, A.M. (In press). Interpersonal Well Being and Mental Health Among Male Partners of Women with Breast Cancer. Issues in Mental Health Nursing

Segrin, C., Badger, T.A., Meek, P., Lopez, A.M., Bonham, E., & Sieger, A.  (in press) Dyadic interdependence on affect and quality of life trajectories among women with breast cancer and their partners.  Journal of Social and Personal Relationships.

Collaborative Research: 

Biography: 

Summary of Research Activity:

Selected Publications: 

Collaborative Research: 

Biography: 

Summary of Research Activity:

Selected Publications: 

Collaborative Research: 

Biography: 

Summary of Research Activity:

Selected Publications: 

Collaborative Research: 

Biography: 

Summary of Research Activity:

My research is directed at the development of knowledge-guided procedures in diagnostic histopathology in two major areas: the implementation of a fully autonomous machine vision system for the evaluation of histo-pathologic sections, and the design of diagnostic decision support systems for histopathology.

The machine vision system allows automated detection and delineation of regions of histologic abnormality in a section; automated scene segmentation followed by histometric and karyometric diagnostic clue extraction; and determination of a numeric, statistically secured progression index for a lesion. This system has been implemented for the processing of colonic lesions, prostatic intraepithelial neoplastic lesions (PIN), malignant lesions of the prostate, breast lesions, and non-melanoma lesions of the skin.

The diagnostic decision support systems are based on inference networks augmented by automated reasoning for process control. These systems have been applied to the assessment of fine needle aspirate specimens from the breast, sections of PIN lesions and malignant prostatic lesions, and benign proliferating lesions of the breast. The systems also are used in the development of decision procedures in automated primary screening devices for cervical cancer.

Selected Publications: 

• Bartels PH, Gahm T, Thompson D. Automated microscopy in diagnostic histopathology: from image processing to automated reasoning. International Journal of Image Systems and Technology 8:214-223, 1997.
• Bartels PH, Thompson D, Montironi R. Knowledge-based image analysis in the precursors of prostatic adenocarcinoma. Eur Urology 30:234-242, 1996.
• Bartels PH, Thompson D, Weber JE. Diagnostic and prognostic decision support systems. Pathologica 87:115-130, 1995.

Collaborative Research: 

• R. Montironi, M.D., Dept. of Pathology, University of Ancona, Italy: quantitative histopathologic assessment of prostatic lesions.
• G.M. Mariuzzi, M.D., Dept. of Pathology, University of Verona, Italy: benign proliferative lesions of the breast.
• P. Hamilton, Ph.D., Dept. of Pathology, Queens University, Belfast, U.K.: decision support systems in histopathology.
• J. Sloan, M.D., Dept. of Pathology, Queens University, Belfast, U.K.: quantitative assessment of adenomatous colonic lesions.
• W. Abmayr, Ph.D., Dept. of Informatics, University of Munich, Germany: inference networks in diagnostic decision support systems.

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At least 90 percent of colorectal cancer deaths can be attributed to lifestyle factors, including diet and smoking, and are potentially preventable. A high-fat diet is a likely major cause of colon cancer. Bile acids are produced by the body to aid in digestion of fats and are known to be promoters of colon cancer. Cells that are excessively damaged by bile acids undergo a controlled process of cell death referred to as apoptosis. This process is beneficial to the body because it removes cells with unrepaired DNA damages; such damaged cells, when allowed to survive, tend to mutate and give rise to cancer. While we and others have found that colonic cancer cells are defective in apoptosis, we also found that the normal-appearing, flat colonic tissue of individuals in high-risk groups is deficient in its ability to undergo apoptosis as well. This appears to be a precancerous change in these high-risk individuals.

We have found that bile acid treatment of cells induces changes in the levels of proteins involved in the cell's response to stress. These protein changes may reflect an effort by the cell to protect itself against damages that otherwise would cause apoptosis, or they may be part of the pathway of apoptosis itself. The apoptosis-resistant cells that are found in normal-appearing colonic tissue of high-risk individuals would be expected to differ from apoptosis-competent cells in the expression of these stress proteins. Since the expression of these specific proteins can be measured accurately and specifically using an automated staining system and computerized imaging program in routinely prepared biopsy specimens, we hypothesize that they should prove useful as biomarkers for colon cancer risk.

We have chosen seven specific genes that we expect may have an altered level of expression in cells resistant to apoptosis. We have shown that each of these gene products is induced by bile acids. The seven gene products to be examined are GRP78 and Hsp70 (chaperone proteins responsive to protein unfolding); NFkB and c-fos (responsive to oxidative stress); GADD153 and PARP (responsive to DNA damage); and iNOS (elevated in colon cancers). A major goal of our research is to test the feasibility of using altered patterns of expression of these genes as a practical biomarker for assessing colon cancer risk. We also expect our research to significantly increase our understanding of the early stages of colon carcinogenesis before gross lesions are detectable.

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• Bernstein C, Bernstein H, Garewal H, Dinning P, Jabi R, Sampliner RE, McCuskey MK, Panda M, Roe D, L'Heureux L, Payne CM. A bile acid-induced apoptosis assay for colon cancer risk, and associated quality control studies. Cancer Res 59:2353-2357, 1999.
• Washo-Stultz D, Hoglen N, Bernstein H, Bernstein C, Payne CM. Role of nitric oxide and peroxynitrite in bile salt-induced apoptosis: relevance to colon carcinogenesis. Nutrition and Cancer 35:193-202, 1999.
• Crowley CL, Payne CM, Bernstein H, Bernstein C, Roe D. The NAD* precursors, incotinic acid and nicotinamide protect cells against deoxycholate induced apoptosis, increase levels of glyceraldehyde-3-phosphate dehydro-genase and decrease constitutive levels of activated NF-kB and GRP78. Cell Death Diff. 7:314-326, 2000.

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• Claire Payne, Ph.D., Microbiology and Immunology: resistance to bile acid induced apoptosis
• Carol Bernstein, Ph.D., Microbiology and Immunology: resistance to bile acid induced apoptosis
• Harinder Garewal, M.D., Ph.D., Medicine: resistance to bile acid induced apoptosis
• Richard Sampliner, M.D., Medicine: resistance to bile acid induced apoptosis

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• Our laboratory provides comparative pathology support for the characterization of rodent models of cancer, with an emphasis on genetically-modified murine models of gastrointestinal cancer.

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• Gerner EW, Ignatenko NA, Besselsen DG . (2003). Preclinical Models for Chemoprevention of Colon Cancer. Recent Results in Cancer Research 163: 58-71.

• Boivin GP, Washington K, Yang K, Ward JM, Pretlow TP, Russell R, Besselsen DG , Godfrey VL, Doetschman T, Dove WF, Pitot HC, Groden J, Coffey RJ. (2003). Pathology of mouse models of intestinal cancer: Consensus report and recommendations. Gastroenterol. 124:762-777.
• two genetically altered rodent models of gastrointestinal carcinogenesis involves deregulation of polyamine synthesis. In: COST 917: Biogenically Active Amines in Food, volume III, Polyamines, the Gut and Cancer (Milovic V and Stein J, eds), Office for Official Publications of the European Communities, Luxembourg .
  
• Wu RS, Kobie JJ, Besselsen DG , Font TC, Mack VD, McEarchern JA, Akporiaye ET. (2001). Comparative analysis of IFN- g , B7.1 and antisense TGF-ß gene transfer on the tumorigenicity of a poorly immunogenic metastatic mammary carcinoma. Canc. Immunol. Immunotherapy 50:229-240.
  
• McEarchern JA, Kobie JJ, Mack V, Wu RS, Meade-Tollin L, Arteaga CL, Dumont N, Besselsen D , Seftor E, Hendrix MJ, Katsanis E, Akporiaye ET. (2001). Invasion and metastasis of a mammary tumor involves TGF- b
  signaling. Inter. J. Canc. 91(1):76-82.
  
• McEarchern JA, Besselsen DG , Akporiaye ET. (1999). Interferon- g and Antisense TGF- b Transgenes Synergize to Enhance the Immunogenicity of a Murine Mammary Carcinoma. Canc. Immunol. Immunotherapy 48:63-70.

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• Emmanuel Akporiaye, Ph.D. Microbiology & Immunology
• Eugene Gerner, Ph.D. Radiation Oncology
• Natalia Ignatenko, Ph.D. Radiation Oncology
• Peter Lance, M.D. Medicine
• Jesse Martinez, Ph.D. Radiation Oncology
• Claire Payne, Ph.D. Microbiology & Immunology
• Mark Nelson, Ph.D. Pathology

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Developmental regulation of the cell cycle; DNA replication; Drosophila as a cancer model.

Our lab is interested in understanding how cell cycle events (such as DNA replication, chromosome segregation and cell growth and cytokinesis) are controlled and modified by development. In multicellular organisms, the ordered events leading to cell proliferation are developmentally constrained or modified so as to be coordinated with important steps in tissue formation. Without these constraints, tissues would fail to grow appropriately, fail to fully develop, and possibly become refractory to anti-proliferative signals. Despite the fundamental role development plays in modifying cell cycle control, there is little known about the factors that coordinate cell cycle events with the spatial and temporal constraints of development. In many human cancers, these constraints have been lost and cells undergo unchecked proliferation. We would like to understand how tissue specific cell cycles are regulated, and thus shed light on how tissue specific tumors arise in humans.

Although we are interested in many aspects of the cell division cycle, our current studies are focused on the control of DNA replication in the Drosophila ovary. Ovarian follicle cells undergo two striking developmentally controlled cell cycle modifications. First, the follicle cells undergo three endo cycles (repeated rounds of DNA replication in the absence of mitosis and cytokinesis ). Second, in response to unknown developmental signals these cells synchronously initiate a gene amplification event that continues to increase the copy number of four different loci. These four sites re-initiate replication while all other genomic replication origins are inactive. Thus, this system will allow us to answer fundamental questions about DNA replication and how it is differentially controlled during development. We have discovered that the Drosophila homolog of the human retinoblastoma tumor suppressor (pRB) is involved in controlling both endo cycles and gene amplification. However, we do not know what developmental factors regulate the fly pRB pathway and instruct cells to shut off DNA replication. We are using a combination of genetic, biochemical, and cell biological techniques