COMPARATIVE CANCER BIOLOGY TRAINING PROGRAM

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: ANIMAL HEALTH
• Reporting Frequency: Annual
• Accession No.: 0224654
• Project Start Date: Oct 1, 2010
• Project End Date: Sep 30, 2012
• Program Code: [(N/A)]- (N/A)

Recipient Organization
CORNELL UNIVERSITY
(N/A)
ITHACA,NY 14853

Performing Department
Biomedical Sciences

Non Technical Summary
This proposal is to establish a comprehensive interdisciplinary training program in comparative cancer biology. This program is designed to address a clear need for structured training in cancer research for both basic and clinical trainees. A broader goal for the proposed program is to establish an organizational structure for cancer research at the Veterinary College that will bring together basic and clinical scientists and promote synergistic interactions with other investigators from throughout Cornell University. The training program includes 27 faculty trainers from the College of Veterinary Medicine, including both basic and clinical faculty. Funding to partially support 2 predoctoral trainees and 3 residents is requested. These trainees were selected from a pool of 31 candidates who were nominated by faculty trainers. Among the nominees are 12 individuals with DVM or BVSc degrees. Selection of trainees for support and general oversight of the Program will be performed by an Executive Committee that includes two basic research trainers, two clinician trainers, and one external advisor. The Executive Committee will seek to evenly distribute funding between basic and clinical trainees. The training program will emphasize rigorous, hypothesis-driven cancer research. Trainees will benefit from a dual mentoring arrangement in which each trainee has both a primary faculty trainer and a co-mentor. Basic research trainees will have a clinical co-mentor and will be required to participate in clinically oriented educational activities. Conversely, clinical trainees will have a basic scientist as co-mentor and will be required to participate in basic science educational activities. Each trainee will be required to give a presentation on their research project at least twice during the funding period and to submit an annual progress report. New comparative cancer biology activities to be developed include designated cancer biology seminars (generously supported by several Units in the College) and associated journal clubs designed to familiarize trainees with the literature related to the seminar topic. In addition, the training program will feature two major cancer research retreats that will gather faculty trainers and trainees for research presentations and discussions, as well as informal interactions. Select cancer researchers from other Departments on the Ithaca campus and from Weill Cornell Medical College will be invited to attend the retreats as an important step toward establishing a broader cancer program that fully leverages the strengths in cancer research at our University, include basic molecular mechanisms, animal models, the physical sciences, and veterinary and human medicine. This training program will establish a much-needed organizational structure that will greatly enhance cancer research at Cornell, with benefits for food and fiber animal as well as human health.

Animal Health Component

(N/A)

Research Effort Categories

Basic

(N/A)

Applied

(N/A)

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
305	3299	1160	10%
305	3499	1160	10%
305	3830	1160	10%
305	3899	1160	20%
311	3299	1160	10%
311	3499	1160	10%
311	3830	1160	10%
311	3899	1160	20%

Knowledge Area
311 - Animal Diseases; 305 - Animal Physiological Processes;

Subject Of Investigation
3499 - Dairy cattle, general/other; 3299 - Poultry, general/other; 3899 - Other animals, general; 3830 - Pets (companion animals);

Field Of Science
1160 - Pathology;

Keywords

cancer

veterinary medicine

training program

Goals / Objectives
The specific objectives of the program are to: 1) provide inter-disciplinary training in comparative cancer biology for a broad group of trainees; 2) create a organized structure for cancer research activities at the College; 3) promote sustainable interactions between basic and clinical cancer researchers; and 4) establish an active cancer community that can interface with colleagues in other Units at Cornell. We expect that the proposed training will lead to the accelerated development of new and more effective methods of veterinary disease detection, prevention and treatment. We further anticipate that the scientific training of basic and clinical trainees at an early stage of their careers will have a significant positive impact on the profession and on animal health and well being in general. We intend that the long-term impact of the program will be to increase the number of professional scientists engaged in animal health-related cancer research.

Project Methods
The proposed training program is designed to educate trainees in cancer biology in the broadest sense, encompassing cell-based systems, animal models, and veterinary and human medicine. Funding is provided to partially support the stipend and research expenses of selected trainees. The program is designed to be inter-disciplinary, with each trainee guided by both basic and clinical faculty trainers. Each trainee is expected to complete a hypothesis driven research project that will withstand the scientific scrutiny of manuscript and grant peer reviewers. Trainees will participate in a variety of training experiences, including bi-annual cancer biology scientific retreats. In sum, this program will provide a well-rounded training experience in cancer biology that includes both basic and clinical elements. In addition to informal discussions with the program organizers, faculty trainers and trainees will have the opportunity to provide feedback at the bi-annual cancer retreats, which will include discussions about the training program. Furthermore, both trainers and trainees will be asked for feedback about the program as part of an annual progress report. Input from trainers and trainees will be assessed by the training program Executive Committee, which includes the co-Program Directors (Drs. Margaret McEntee and Robert Weiss), a basic science trainer (Dr. Rick Cerione), a clinical trainer (Dr. Gerald Duhamel), and an external advisor (Dr. David Putnam, Department of Biomedical Engineering). This group additionally will review research plans from each trainee, observe trainee presentations at the research retreats, and read the annual progress reports from the trainees. If any deficiencies or shortcomings are noted, the Executive Committee will be charged with making recommendations for corrective actions. As noted in the training plan, the Executive Committee also will provide constructive feedback to trainers and trainees as part of the annual review process. This will include a written document highlighting the strengths and weaknesses of the training and research activities for the trainee.

Progress 10/01/10 to 09/30/12

Outputs
OUTPUTS: The specific objectives of the Comparative Cancer Biology Training Program (CCBTP) at the Cornell Univ College of Veterinary Medicine (CVM) are to: 1) provide inter-disciplinary training in comparative cancer biology for a broad group of trainees; 2) create an organized structure for cancer research activities at the College; 3) promote sustainable interactions between basic and clinical cancer researchers; and 4) establish an active cancer community that can interface with colleagues in other Units at Cornell. With funding from the USDA and matching internal funds we made strong progress toward achieving these goals, during the second year of support. The major events organized by the program in year 2 included the following: A. CORNELL UNIV TRANSLATIONAL CANCER BIOLOGY SYMPOSIUM The Symposium was held on October 1, 2011 on the campus of Cornell Univ in Ithaca, NY. The event was organized jointly by The CCBTP at CVM, together with Cornell Center on the Microenvironment & Metastasis, Weill-Cornell Medical College and the Methodist Hospital Cancer Center. The objective of the Symposium was to bring together researchers from the Cornell life science, physical science, and medical (veterinary and human) communities who have complementary expertise and common interests in cancer biology. The event featured sessions on Imaging & Diagnostics and Molecular Mechanisms and Therapeutics. There was a keynote address by Dr. David Piwnica-Worms (Washington Univ), research presentations by faculty associated with each of the participating programs, and a poster session. The full event schedule and additional program details can be found at the following website: http://cmm.cornell.edu/events/translational-cancer-research-symposium .html B. FALL CANCER BIOLOGY SEMINAR MINI-SERIES In the Fall of 2012, the CCBTP, with additional support from the Baker Institute and the Departments of Biomedical Sciences, Clinical Sciences, Microbiology & Immunology, and Molecular Medicine, organized and hosted a series of cancer-focused seminars at the CVM. The speakers were as follows: DR. CHAND KHANNA, National Cancer Institute A Comparative Approach to Cancer Biology and Therapy DR. ALEA A. MILLS, Cold Spring Harbor Laboratory CHD5: Chromosome Engineering, Chromatin Dynamics, and Cancer DR. RALPH DEBERARDINIS, Univ of Texas - Southwestern Medical Center Intermediary Metabolism and Cancer: Cell Biology and Translational Opportunities DR. CHERYL LONDON, The Ohio State Univ Spontaneous Cancer in Dogs: Opportunities for Preclinical Evaluation of Novel Therapeutics DR. YUAN CHANG, Univ of Pittsburgh Cancer Institute Using Viral Genomics to Find Causes and Potential Cures for Human Cancers DR. JEFFREY A. TORETSKY, Georgetown Univ Medical Center Small-molecule Targeting of Fusion Protein Transcription Factors and the Biochemistry of Intrinsically Disordered Proteins C. Comparative Cancer Biology Training Program WIP session A Work-in-Progress (WIP) meeting for The CCBTP was held on Friday December 21, 2012. This gathering featured short scientific talks (~10-15 minutes each) by 4 of the supported trainees: Erika Gruber, Gongshi Bai, Sachi Horibata, and Vanessa Rizzo. PARTICIPANTS: The following Cornell Univ College of Veterinary Medicine trainees participated in the training program. Each is listed along with the name of their primary faculty mentor. Gongshi Bai, Graduate student in Genetics & Development (Mentor: Dr. John Schimenti) Erika Gruber, Resident in Clinical Pathology (Mentor: Dr. Tracy Stokol) Sachi Horibita, Graduate student in Pharmacology (Mentor: Dr. Scott Coonrod) Chang-il Hwang, Postdoctoral fellow (Mentor: Dr. Alex Nikitin) Yunxing (Stella) Li, Graduate student in Biophysics (Mentor: Dr. Rick Cerione) Pei Xin Lim, Graduate student in Genetics & Development (Mentor: Dr. Robert Weiss) Brendan Noonan, Resident in Avian Medicine and Surgery (Mentor: Dr. Ricardo de Matos) Vanessa Rizzo, Resident in Medical Oncology (Mentor: Dr. Joe Wakshlag) TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
A primary role for the Comparative Cancer Biology Training Program was to provide financial backing for the cancer research and career development activities of several trainees. Using funding from the USDA and matching internal funds, the Program was able to partially support the stipend and/or research expenses of 8 trainees in year two. The individuals are named below, under "participants". We also established an important new programmatic connection with the Cancer Resource Center of the Finger Lakes, a community group that provides support and resources to cancer patients and survivors. In conjunction with Mr. Bob Riter, Executive Director of the Cancer Resource Center, a new mechanism for trainees in the Comparative Cancer Biology Training Program to engage in outreach activities associated with the CRC. The goal of this initiative is to provide opportunities for trainees to meet with cancer patients, survivors, and advocates in order to learn about cancer from their perspective and to discuss some of the cancer research activities underway at Cornell. Currently, several trainees attend weekly or bi-weekly cancer support group meetings with community members.

Publications

• Chuang CH, Yang D, Bai G, Freeland A, Pruitt SC, Schimenti JC. Post-transcriptional homeostasis and regulation of MCM2-7 in mammalian cells. Nucleic Acids Res. 2012 Jun;40(11):4914-24. doi: 10.1093/nar/gks176. Epub 2012 Feb. PMID: 22362746.
• Mohanan S, Horibata S, McElwee JL, Dannenberg AJ, Coonrod SA. Identification of macrophage extracellular trap-like structures in mammary gland adipose tissue: a preliminary study. Front Immunol. 2013;4:67. doi: 10.3389/fimmu.2013.00067. Epub 2013 Mar 18. PMID: 23508122.
• Mohanan S, Cherrington BD, Horibata S, McElwee JL, Thompson PR, Coonrod SA. Potential role of peptidylarginine deiminase enzymes and protein citrullination in cancer pathogenesis. Biochem Res Int. 2012;2012:895343. Epub 2012 Sep 16. PMID:23019525
• Horibata S, Coonrod SA, Cherrington BD. 2012 Role for peptidylarginine deiminase enzymes in disease and female reproduction. J Reprod Dev. ;58(3):274-82. Review. PMID: 22790870.
• Flesken-Nikitin A, Hwang CI, Cheng CY, Michurina TV, Enikolopov G, Nikitin AY. Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature. 2013 Mar 14;495(7440):241-5. doi: 10.1038/nature11979. Epub 2013 Mar 6. PMID: 23467088.
• Gu X, Vedvyas Y, Chen X, Kaushik T, Hwang CI, Hu X, Nikitin AY, Jin MM. Novel strategy for selection of monoclonal antibodies against highly conserved antigens: phage library panning against ephrin-B2 displayed on yeast. PLoS One. 2012;7(1):e30680. doi: 10.1371/journal.pone.0030680. Epub 2012 Jan 23. PMID: 22292016.
• Hwang CI, Choi J, Zhou Z, Flesken-Nikitin A, Tarakhovsky A, Nikitin AY. MET-dependent cancer invasion may be preprogrammed by early alterations of p53-regulated feedforward loop and triggered by stromal cell-derived HGF. Cell Cycle. 2011 Nov 15;10(22):3834-40. doi: 10.4161/cc.10.22.18294. Epub 2011 Nov 15. PMID: 22071625.
• Hwang CI, Matoso A, Corney DC, Flesken-Nikitin A, Korner S, Wang W, Boccaccio C, Thorgeirsson SS, Comoglio PM, Hermeking H, Nikitin AY. Wild-type p53 controls cell motility and invasion by dual regulation of MET expression. Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14240-5. doi: 10.1073/pnas.1017536108. Epub 2011 Aug 9. PMID:21831840
• Lyndaker AM, Lim PX, Mleczko JM, Diggins CE, Holloway JK, Holmes RJ, Kan R, Schlafer DH, Freire R, Cohen PE, Weiss RS. Conditional Inactivation of the DNA Damage Response Gene Hus1 in Mouse Testis Reveals Separable Roles for Components of the RAD9-RAD1-HUS1 Complex in Meiotic Chromosome Maintenance. PLoS Genet. 2013 Feb;9(2):e1003320. doi: 10.1371/journal.pgen.1003320. Epub 2013 Feb 28. PMID: 23468651.