researchers
Mark Alexandrow, PhD
2006
$27,500
Progress Report Summary: The funds received were primarily used to support my Cancer Biology graduate student, Philip G. Wong, who has recently graduated with his Ph.D. degree (fall 2010). The Award supported Phil's projects and some other lab projects, which directly contributed to several published peer reviewed papers in high quality journals. These papers, and others supported in part by the Miles funding, are listed below. The Award was also instrumental in supporting research that lead to my lab obtaining several national grants from the National Cancer Institute (NIH). The first grant was one in which I was co-PI with the former head of Thoracic Oncology (Gerold Bepler, M.D.) on a lung cancer chemoprevention trial as part of the first ever SPORE awarded to Moffitt and the State of Florida (Lung Cancer Chemoprevention by Enzastaurin, 1P50-CA119997, ~$10.5 million total award). Overall, the SPORE scored the highest in the U.S. of all SPORES on all tumor topics, and our trial within the SPORE received one of the highest scores of all of the four projects. I am the PI on two other awards from the NCI. One is an R01 (Chromatin Remodeling by Cdt1: Role in DNA Replication and Tumorigenesis, 1R01-CA130865, ~$1.8 million total award to my group) and the other is an R21 that scored in the 1st percentile on the first submission (MCM Helicase as a Novel Target for Pancreatic Cancer Treatment, R21-CA155393, ~$450,000 total award). I also have two R01 grants pending funding or review from the NCI (Function of the Mcm7-Rb Interaction in Growth Factor Signaling and Tumorigenesis, 1R01-CA125059, ~$2.1 million total; Phase II Chemoprevention Trial of Curcumin in Former Smokers, co-PIs: Nagi Kumar, Mark Alexandrow, and Jhanelle Gray, R01-CA160270, ~$3.7 million total). All of my projects, grants, and papers focus on understanding how the DNA replication machinery is controlled during normal and tumor growth, specifically proteins known as the pre-Replication Complex that sit at and regulate origins of DNA replication when cells decide to start copying their chromosomes. We have a long term goal of designing drugs to one or more of the preRC proteins we study, based on our molecular understanding of their functions in growth control.
Grants:
7/1/10-4/30/15 National Institutes of Health, National Cancer Institute
R01 CA131398-01
“Chromatin Remodeling by Cdt1: Role in DNA replication and Tumorigenesis”
Direct: $933,750 Total: $1,559,365
1/1/11-12/31/12 National Institutes of Health, National Cancer Institute
R21 CA155393-01
“MCM Heliase as a Novel Target for Pancreatic Cancer Treatment”s”
Direct: $275.000 Total: $459,250
Publications:
Chang-Gong Lee, Michael Gruidl, Steven Eschrich, Susan McCarthy, Hong-Gang Wang, Mark G. Alexandrow, and Timothy J. Yeatman. 2008. Cholesterol Regulator Insig-2 Promotes Colon Tumorigenesis and Inhibits Bax-Mediated Apoptosis. Inter. J. Cancer., 123:273-282. PMCID: PMC2650850
Piyali Mukherjee, Thinh V. Cao, Sherry L. Winter, and Mark G. Alexandrow. 2009. Mammalian MCM Loading in Late-G1 Coincides with Rb Hyperphosphorylation and the Transition to Post-Transcriptional Control of Progression into S-phase. PlosONE, 4:e5462. PMID: 19421323; PMCID: PMC2674209
Wasia Rizwani, Mark G. Alexandrow, and Srikumar Chellappan. 2009. Prohibitin physically interacts with MCM proteins and inhibits mammalian DNA replication. Cell Cycle, 8:1621-1629. PMID: 19377303
Piyali Mukherjee, Sherry L. Winter and Mark G. Alexandrow. 2010. Cell Cycle Arrest by TGFß1 Near G1/S Is Mediated by Acute Abrogation of preRC Activation and an Rb-MCM Interaction. Mol. Cell. Biol. 30:845-856. PMID: 19948884
Philip G. Wong, Michele A. Glozak, Thinh V. Cao, Cyrus Vaziri, Edward Seto and Mark G. Alexandrow. 2010. Cdt1 Chromatin Decondensation Regulates MCM Loading Via Opposing Functions of HBO1 and HDAC11-Geminin. Cell Cycle; 9(21):4351-63. PMID: 20980834. News and Views article by Benoit Miotto, 2011, Cell Cycle.
Philip G. Wong*, Sherry L. Winter*, Elena Zaika*, Thinh V. Cao, Umut Oguz, John M. Koomen, Joyce L. Hamlin and Mark G. Alexandrow. 2011. Cdc45 Limits Replicon Usage from a Low Density of preRCs in Mammalian Cells. PlosONE, 6(3):e17533. PMID: 21390258 *co-first authors.
Jong Park, PhD
2006
$25,000
Progress Report Summary:
The Miles for Moffitt award helps me to promote and become a tenured independent scientist. The Miles for Moffitt fund is used for generating promising preliminary data, which were leaded to obtain a large NIH grant. In addition, this fund contributed, directly or indirectly, to publish several articles in peer reviewed scientific journals, 1 book chapter, and 11 abstracts were/will be presented in national and international scientific meetings. Since the Miles for Moffitt award in 2006, the research project titled “Genetic analysis in recurrent prostate cancer” generates several publications, abstracts, book chapter, and national grant were obtained using results generated from this support.
Grants:
7/15/08-6/30/13 National Institutes of Health, National Cancer Institute
R01 CA128813
“Genetic & epigenetic analysis of angiogenesis genes in recurrent prostate cancer”
Direct: $1,267,721 Total: $2,108,879
Publications:
Park JY, Tanner JP, Sellers TA, Huang Y., Stevens CK, Dossett, N., Shankar, RA., Zachariah, B., Heysek, R., and Pow-Sang, J. (2007). Association between polymorphisms in HSD3B1 and UGT2B17 and prostate cancer risk. Urology 70(2):374-379. PMID: 17826523.
Park, JY, Zheng, W, Kim DH, Cheng, JQ, Kumar, N, Ahmad, N, and Pow-Sang, J. Candidate tumor suppressor gene SLC5A8 is frequently down regulated by promoter hypermethylation in prostate tumor. Cancer Detection and Prevention, 2007, 31(5):359-365. PMID: 18037591.
Park JY, Huang Y, and Sellers TA. Single nucleotide polymorphisms in DNA repair genes and prostate cancer risk. Methods in Molecular Biology. 2009, 471:361-385. PMID: 19109789.
Eeles RA, Kote-Jarai Z, Al Olama AA, Giles GG, Guy M, Severi G, Muir K, Hopper JL, Henderson BE, Haiman CA, Schleutker J, Hamdy FC, Neal DE, Donovan JL, Stanford JL, Ostrander EA, Ingles SA, John EM, Thibodeau SN, Schaid D, Park JY, Spurdle A, Clements J, Dickinson JL, Maier C, Vogel W, Dörk T, Rebbeck TR, Cooney KA, Cannon-Albright L, Chappuis PO, Hutter P, Zeegers M, Kaneva R, Zhang HW, Lu YJ, Foulkes WD, English DR, Leongamornlert DA, Tymrakiewicz M, Morrison J, Ardern-Jones AT, Hall AL, O'Brien LT, Wilkinson RA, Saunders EJ, Page EC, Sawyer EJ, Edwards SM, Dearnaley DP, Horwich A, Huddart RA, Khoo VS, Parker CC, Van As N, Woodhouse CJ, Thompson A, Christmas T, Ogden C, Cooper CS, Southey MC, Lophatananon A, Liu JF, Kolonel LN, Le Marchand L, Wahlfors T, Tammela TL, Auvinen A, Lewis SJ, Cox A, Fitzgerald LM, Koopmeiners JS, Karyadi DM, Kwon EM, Stern MC, Corral R, Joshi AD, Shahabi A, McDonnell SK, Sellers TA, Pow-Sang J, Chambers S, Aitken J, Gardiner RA, Batra J, Kedda MA, Lose F, Polanowski A, Patterson B, Serth J, Meyer A, Luedeke M, Stefflova K, Ray AM, Lange EM, Farnham J, Khan H, Slavov C, Mitkova A, Cao G; The UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology; The UK ProtecT Study Collaborators; The PRACTICAL Consortium, Easton DF. Identification of seven novel prostate cancer susceptibility loci through a genome-wide association study. Nature Genetics, 2009, 41(10):1116-1121 PMID: 19767753.
Park JY Promoter hypermethylation in prostate cancer. Cancer Control, 2010, 17(4):245-255 PMID: 20861812.
Chang B, Spangler E, Gallagher S, Haiman C, Henderson B, Isaacs W, Benford ML, Kidd LR, Cooney K, Strom SA, Ingles S,
Stern MC, Corral R,
Joshi AD, Xu J, Giri VN, Rybicki B, Neslund-Dudas C, Kibel AS, Thompson IM, Leach RJ, Ostrander EA, Stanford JL, Witte J, Casey G, Eeles R, Hsing,
AW, Chanock S, Hu JJ, John EM, Park JY, Stefflova K, Zeigler-Johnson C,,and Rebbeck TR. Validation of Genome-Wide Prostate Cancer Associations
in Men of African Descent. Cancer Epi. Biom. Prev. 2011, 20(1): 23-32. PMID: 21071540.
Park JY, Ahn J, Kibel A, Rebbeck T, Rennert H, Stanford J., Ostrander E, Chanock S, Wang MH, Mittal RD, Isaacs W, Platz E, and Hayes RB. Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence. Clinical Cancer Research, 2011, 17:1075-1081. PMID: 21343373.
Kote-Jarai Z, Al Olama AA, Giles GG, Severi G, Schleutker J, Weischer M, Canzian F, Riboli E, Key T, Gronberg H, Hunter D, Kraft P, Thun MJ, Ingles S, Chanock S, Albanes D, Hayes RB, Neal DE, Hamdy FC, Donovan JL, Pharoah P, Schumacher F, Henderson BE, Stanford JL, Ostrander EA, Sorensen KD, Dörk T, Andriole G, Dickinson JL, Cybulski C, Lubinski J, Spurdle A, Clements JA, Chambers S, Aitken J, Frank Gardiner RA, Thibodeau SN, Schaid D, John EM, Maier C, Vogel W, Cooney KA, Park JY, Cannon-Albright L, Brenner H, Habuchi T, Zhang HW, Lu YJ, Kaneva R, Muir K, Benlloch S, Leongamornlert DA, Saunders EJ, Tymrakiewicz M, Mahmud N, Guy M, O’Brien LT, Wilkinson RA, Hall AL, Sawyer EJ, Dadaev T, Morrison J, Dearnaley DP, Horwich A, Huddart RA, Khoo VS, Parker CC, Van As N, Woodhouse CJ, Thompson A, Christmas T, Ogden C, Cooper CS, Lophatonanon A, Southey MC, Hopper JL, Tiina Wahlfors ED, Tammela TL, Klarskov P, Nordestgaard BG, Røder MA, Tybjærg-Hansen A, Bojesen SE, Travis R, Campa D, Kaaks R, Wiklund F, Aly M, Lindstrom S, Diver WR, Gapstur S, Stern MC, Corral R, Virtamo J, Cox A, Haiman CA, Le Marchand L, Fitzgerald L, Kolb S, Kwon EM, Karyadi DM, Orntoft TF, Borre M, Meyer A, Serth J, Yeager M, Berndt SI, Marthick JR, Patterson B, Wokolorczyk D, Batra J, Lose F, McDonnell SK, Joshi AD, Shahabi A, Rinckleb AE, Ray A, Sellers T, Lin HY, Stephenson RA, Farnham J, Muller H, Rothenbacher D, Tsuchiya N, Narita S, Cao GW , Slavov C, Mitev V, The UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons’ Section of Oncology, The UK ProtecT Study Collaborators, The PRACTICAL Consortium, Easton DF, Eeles RA. Seven Prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. Nature Genetics. 2011 43(8):785-791. PMID: 21743467
Lin HY, Park HY, Radlein S, Mahajan N, Sellers TA, Zachariah B, Pow-Sang J, Coppola D, Ganapathy V and Park JY. Protein expressions and genetic variations of SLC5A8 in prostate cancer risk and aggressiveness. Urology. 2011, PMID21802122 (in press).
Jia Fang, PhD 2007
$25,000
Progress Report Summary:
Epigenetic silencing of tumor suppressor genes is a common event in carcinogenesis, and often involves aberrant DNA methylation and histone modifications. The goal of my lab is to understand the importance of different epigenetic modifications in human cancer. With supports from Miles for Moffitt and other grants, we have recently characterized a novel histone methyl-H3K9 binding protein MPP8. MPP8 expression is elevated in various human tumor cells, while knocking-down MPP8 in breast cancer cells leads to the loss of cellular mesenchymal marker as well as the reduction of tumor cell migration and invasiveness. These results suggest that MPP8 promotes epithelial-to-mesenchymal transition (EMT) and could in turn contribute to breast cancer progression and metastasis. At molecular level, we further demonstrated that MPP8 directly targets the E-cadherin promoter and represses expression of this key regulator of EMT and tumor progression by coupling H3K9 methylation and DNA methylation. Given that the aberrant activation of EMT is an essential mechanism to endow cancer cells with invasive and metastatic competence, our findings provide important insights into the early steps of cancer metastasis and thus have therapeutic values.
Grants:
7/1/08-6/30/11 Florida Department of Health, Bankhead Coley
08BN-01-17192
“Role of Novel Methyl-H3K9 Binding Protein MPP8 in Transcription Silencing and Tumorigenesis
Direct: $347,222 Total: $375,000
Publications:
Kokura K and Fang J*. In Vitro Histone Demethylase Assays. Methods Mol Biol., The Human Press Inc. 2009, 523:249-261
Li Z, Chen L, Kabra N, Wang C, Fang J* Chen J. Inhibition of SUV39H1 methyltransferase activity by DBC1. J Biol Chem., 2009, 284(16):10361-10366
Kokura K, Sun L, Bedford MT, Fang J*. Methyl-H3K9-binding protein MPP8 mediates E-cadherin gene silencing and promotes tumour cell motility and invasion. EMBO J., 2010, 29:3673-3687
Sun L, Fang J*, Writer Meets Eraser in HOTAIR. Acta Biochim Biophys Sin., 2011, 43:1-3.
Prakash Chinnalyan, MD
2007
$25,000
Progress Report Summary
As an early-career physician-scientist, support from the Miles for Moffitt Award has been critical for my continued development as a cancer researcher. The overarching goal of our laboratory is to contribute towards the advancement in the understanding of brain tumor biology and clinical improvement in brain tumor patients. Specifically, this award has provided support to bring an additional member into my laboratory, and with this, the scientific freedom to explore novel areas of cancer research. Based on this addition, critical preliminary data was generated, leading directly towards my success in obtaining continued research funding. Specific successful applications include a recent award from the American Cancer Society (4 years, $720,000), the Ben and Catherine Ivy Foundation (1 yr, $150,000), and the US Army (1 yr, $160,000). I am hopeful that this generous support will serve as the foundation for my continued cancer research through the course of my career.
Grants:
1/1/11-12/31/14 American Cancer Society
RSF 1102901CSM
“Modulating the Unfolded Protein Response Through Grp78 Acetylation”
Direct: $600,000 Total: $720,000
Publications:
Chinnaiyan P, Wang M, Rojiani AM, Tofilon PJ, Arnab Chakravarti A, Ang KK, Zhang H, Hammond E, Curran W, Mehta MP. “The Prognostic Value of Nestin Expression In Newly Diagnosed Glioblastoma: Report From The RTOG.” Radiat Oncol. 2008 Sep 25;3:32. PMID: 18817556
Kahali S, Sarcar B, Fang B, Williams ES, Koomen JM, Tofilon PJ, Chinnaiyan P,. “Activation of the unfolded protein response contributes toward the antitumor activity of vorinostat. ” Neoplasia. 2010 Jan;12(1):80-6. PMID: 20072656
Sarcar B, Kahali S, Chinnaiyan P,. “Vorinostat enhances the cytotoxic effects of the topoisomerase I inhibitor SN38 in glioblastoma cell lines.” J Neurooncol. 2010 Sept;99(2):201-7. PMID: 20135194
Sarcar B, Kahali S, Chinnaiyan P,. “The Emerging Role of Histone Deacetylases (HDACs) in Unfolded Protein Response Regulation.” Methods Enzymol. 2011;490:159-74. PMID: 21266250.
Chinnaiyan P, Backer MV, Backer JM. “Targeting the Unfolded Protein Response in Cancer Therapy.” Methods Enzymol. 2011;491:37-56. PMID: 21329793 
Susan Vadaparampil, PhD
2007
$25,000
Progress Report Summary
Since receiving this award, I have been able to extend my research in two primary scientific areas in women’s oncology: dissemination of HPV vaccination as a method of reducing cervical cancer incidence and promoting risk appropriate uptake of genetic counseling and testing for hereditary breast and ovarian cancer among high risk women. With respect to my interests related to HPV vaccination, I secured an R01 in July of 2008 to identify patterns of recommendation of HPV vaccination among a national sample of U.S. physicians and a Moffitt-UF Partnership grant focusing on parent, patient, and provider factors impacting uptake of HPV vaccination in underserved adolescent females. With regard to my interests in genetic testing for hereditary breast and ovarian cancer, In July 2011, I was awarded a 5-year Research Scholar Grant from the American Cancer Society to evaluate the impact of BRCA testing on psychosocial functioning and risk reduction behaviors in a population-based sample of 600 African American women with early onset breast cancer. Additionally, I will likely receive funding for an R21 to develop and pilot test an intervention to increase uptake of genetic counseling and testing among recently diagnosed breast cancer patients. Finally, in August of 2011, my colleague and I obtained funding for a 5-year NCI-funded R25 national training grant (Multiple PIs: Quinn and Vadaparampil) that will provide an opportunity for oncology nurses in several areas of reproductive health that are relevant to women’s oncology. Additionally, I serve as a co-investigator on numerous projects with colleagues across the cancer center. I am pleased that the theme of health disparities and access to care are a fundamental basis for my entire research program.
Since the time I received the Miles for Moffitt Award, I have also made steady progress in my overall academic career. During my career I have published 79 articles in peer-reviewed journals, 60 of which have published since January 2008. Throughout this time, I have worked with numerous trainees during this time as a research supervisor, primary mentor, or committee member. I am also currently mentoring my first post doctoral fellow. As recognition of my growing national reputation in the field of cancer prevention and control, I was named as a charter member to an NIH peer review committee in 2011. Since 2008, I have served on the editorial board of the NCI’s Cancer Genetics PDQ Editorial Board. In 2011 our editorial board received an NIH Team Merit Award which recognizes the PDQ Board’s dedicated and exceptional service in maintaining evidenced-based information summaries for health professionals and the public. Finally, I have been actively involved in outreach and education. Most recently, I secured an educational grant from the Florida Breast Cancer Foundation to expand efforts to increase awareness about hereditary breast and ovarian cancer in the African American community using a community-academic partnership model. These accomplishments highlight my efforts to continually grow in the areas of research, teaching, professional service and community service. My promotion to Associate Professor in 2009 provides recognition of these efforts from the Moffitt academic community.
Grants:
7/2/08-6/30/12 National Institutes of Health, NAID
R01 AI076440-01A1
“Recommendation of HPV Vaccination Among U.S. Physicians”
Direct: $1,415.747 Total: $2,066.163
7/1/11-6/30/16 American Cancer Society
RSG 11 268 01-CPPB
“Behavioral and Emotional Impact of BRCA Testing in African Americans (BENITA)”
Direct: $752,500 Total: $903,000
Publications:
Lipkus I, Vadaparampil ST, Jacobsen PB, Miree CA. (2011) Knowledge about Genomic Recurrence Risk Testing among Breast Cancer Survivors, accepted, Journal of Cancer Education. [June 19, Epub ahead of print]. PMID: 21688183
Nupam Mahajan, PhD
2008
$25,000
Progress Report Summary
Background Adrogen receptor (AR) plays a critical role in the progression of bothandrogen-dependent and androgen-independent prostate cancer (AIPC). Ligand-independent activation of AR in AIPC or castration resistant prostate cancer (CRPC) is often associated with poor prognosis. Recently, tyrosine kinase Ack1 has been shown to regulate AR activity by phosphorylating it at tyrosine 267 and this event was shown to be critical for AIPC growth. However, whether a small molecule inhibitor that can mitigate Ack1 activation is sufficient to abrogate AR activity on AR regulated promoters in androgen-depleted environment is not known. We have generated two key resources, antibodies that specifically recognize pTyr267-AR and synthesized a small molecule inhibitor of Ack1, 4-amino-5,6-biaryl-furo[2,3-d]pyrimidine (named here as AIM-100) to test whether AIM-100 modulates ligandindependent AR activity and inhibits prostate cell growth.
Results Prostate tissue microarray analysis indicates that Ack1 Tyr284 phosphorylation correlates positively with disease progression and negatively with the survival of prostate cancer patients. Interestingly, neither pTyr267-AR expression nor its transcriptional activation was affected by anti-androgens in activated Ack1 expressing or EGF stimulated prostate cells. However, the Ack1 inhibitor, AIM-100, not only inhibited Ack1 activation but also able to suppress pTyr267-AR phosphorylation, binding of AR to PSA, NKX3.1, and TMPRSS2 promoters, and inhibit AR transcription activity.
Conclusion Tyr284 phosphorylation is prognostic of progression of prostate cancer and inhibitors of Ack1 activity could be novel therapeutic agents to treat AIPC.
Grants:
6/8/10-4/30/15 National Institutes of Health, National Cancer Institute
R01 CA135328-01
“ACK1: A Critical Regulator of Hormone Refractory Prostrate Cancer”
Direct: $867,971 Total: $1,449,511
Publications:
Mahajan K. Mahajan NP, Shepherding Androgen receptor and AKT by Ack1 in hormonally regulated cancers. Journal of Cellular Physiology, 224:327-33, 2010
Mahajan K, Challa S, Coppola D, Lawrence H, Luo Y, Zhu W, and Chen A, Lawrence NJ, Mahajan NP,. Effect of Ack1 Tyrosine Kinase Inhibitor on Ligand-Independent Androgen Receptor Activity. Prostate, 70:1274-1285, 2010
Mahajan K, Coppola D, Challa S, Fang B, Chen A, Zhu W, Lopez AS, Koomen J, Engelman RW, Riviera C, Schönbrunn E, Sebti SM, and Cheng JQ, Earp HS and Mahajan NP,. Tyrosine Phosphorylation Regulates AKT/PKB Function. PLoS ONE, 5:e9646, 2010
Dana Rollison, PhD
2008
$25,000
Progress Report Summary
The Miles for Moffitt Award has been critical in furthering my research on the role of cutaneous viral infections and cancer. My work in this area first began when I received an American Cancer Society (ACS) institutional research grant (IRG) shortly after arriving at Moffitt in 2004 to investigate biomarkers of cutaneous human papillomavirus (HPV) infection among patients with non-melanoma skin cancers (NMSC). Results of that pilot project led to the successful competition for a James and Esther King New Investigator Award funded through the state of Florida’s Biomedical Research Program which enabled me to conduct a case-control study of cutaneous HPV infection in NMSC. Results from the case-control study demonstrated a positive association between antibodies to cutaneous HPV and NMSC. These compelling findings led me to investigate the presence of cutaneous HPV DNA in the tumor tissues themselves. When NMSC patients who had cutaneous HPV DNA present in their tumor tissues were compared to controls, the association with cutaneous HPV antibodies was even stronger. Furthermore, we observed the presence of another cutaneous virus, Merkel cell polyomavirus (MCV), in a subset of NMSC tissues, with higher MCV antibody levels among NMSC cases with MCV DNA in their tumors as compared to controls.
The initial grants from the ACS and state of Florida were instrumental in establishing the infrastructure for recruiting patients and collecting samples. However, the funds provided by Miles for Moffitt facilitated the additional laboratory testing that was not included in the initial project scope, in addition to the statistical analyses of the laboratory test results. The Miles for Moffitt funding facilitated the observation of the correlation between viral DNA with antibody levels and accelerated the overall progress of my research program. This line of research has resulted in multiple publications and abstracts, listed below. The data generated serve as the basis of a prospective cohort study currently being proposed as part of Moffitt’s skin SPORE grant application to be submitted in September.
Grants:
9/1/06-7/31/12 National Institutes of Health, National Cancer Institute
R01 CA118348-03
“Nested Case Study of JC Virus Infections and Incident Colorectal Cancer”
Direct: $708,796 Total: $923,953
Publications:
Rollison DE, Pawlita M, Giuliano AR, Iannacone MR, Sondak VK, Messina JL, Cruse CW, Fenske NA, Glass LF, Kienstra M, Michael KM, Waterboer T, Gheit T, Tommasino M. Measures of cutaneous human papillomavirus infection in normal tissues as biomarkers of HPV in corresponding non-melanoma skin cancers. Int J Cancer, 2008; 123(10):2337-42. PMID: 18729188
Iannacone MR, Pawlita M, Giuliano AR, Waterboer T, Michael KM, Rollison DE. Risk factors for cutaneous HPV seroreactivity among skin cancer screening patients in Florida. J Infect Dis. 2010 Mar 1;201(5):760-9. PMID: 20105078
David Shibata, MD
2008
$25,000
Progress Report Summary
Following the receipt of the 2008 Miles for Moffitt Award, the funds initially contributed to the development to the acquisition of an R01 Research Grant studying the signal transduction and regulation of a novel tumor suppressor gene, HPP1. An R01 award has been used to support promising but not yet funded research initiatives. These include 1) Colorectal cancer gene expression profiling projects and 2) Investigation of miR-675, a novel miRNA that is important in AFP-secreting hepatocellular cancers. Most importantly, the Miles for Moffitt award has allowed us to initiate and sustain transdisciplinary collaborations with Dr. Erin Siegel of the Risk Assessment, Detection and Intervention program. Key collaborative projects that have been supported by the Miles for Moffitt Award include initiatives in 3) The study of adiposity and colorectal cancer 4) Comprehensive analyses of epigenetics and HPV in anal cancer.
Grants:
7/1/09-6/30/14 National Institutes of Health, National Cancer Institute
R01 Research Project Grant, R01 CA131398-01
“STAT1 Activation and HPP1 Tumor Suppression”
Direct: $1,549,562.00 Total: $2,584,729
Publications:
Hernandez JM, Farma JM, Coppola D, Fulp WJ, Chen D-T, Siegel EM, Yeatman TJ. and Shibata D, Expression of the Anti-Apoptotic Protein Survivin in Colon Cancer. Clinical Colorectal Cancer 2011 (Accepted in Press)
Melis M, Hernandez J, Siegel EM, McLoughlin JM, Ly QP, Nair RM, Lewis JM, Jensen EH, Alvarado MD, Coppola D, Eschrich S, Bloom GC, Yeatman TJ and Shibata D,. Gene Expression Profiling of Colorectal Mucinous Adenocarcinomas Dis Colon Rectum. 2010 Jun;53(6):936-43.
Siegel EM, Ulrich CM, Poole EM, Holmes RS, Jacobsen PB and Shibata D. Obesity and Obesity-related conditions and Colorectal Cancer Prognosis. Cancer Control 2010 Jan;17(1):52-7.
Hernandez JM, Elahi A, Siegel EM, Coppola D, Riggs B and Shibata D. HPV L1-Capsid Protein Detection and Progression of Anal Squamous Neoplasia. Amercian Journal of Clinical Pathology 2010 (Accepted- In Press)
Hernandez JM, Siegel EM, Elahi A, Eschrich SA, Coppola D, Riggs B, Grady WM, Giuliano AR and Shibata D. DNA Methylation Profiling Across the Spectrum of HPV-Associated Anal Squamous Neoplasia. Submitted to PLoS ONE 2011.
Hernandez, JM; Siegel, EM; Koch, A; Shibata, D. Chapter 13 Counterpoint: Squamous Cell Carcinoma of the Anus: Surveillance after Treatment in Cancer Patient Follow-up: An international perspective. (Eds) Johnson, FE; Virgo, KS; Margenthaler, JA; and et. Al. 2nd edition, Springer 2011. (In Press)
Van Simmons, PhD
2008
$25,000
Progress Report Summary
The Miles for Moffitt award has been a wonderful stepping stone in my career trajectory. The funds from this award were used to supplement my funding from NCI to conduct a study on smoking relapse among lung and head and neck cancer patients. To date, one article has been published and one is in press from the data collected from this study. The results from this study were also used to support an R01 grant application to test a smoking relapse-prevention intervention for cancer patients. I am happy to report that this application was funded and began just a few months ago. Overall, the funds were instrumental in helping me to build a programmatic line of research to help cancer patients to maintain their smoking abstinence.
Grants:
3/1/11-2/28/12 National Institutes of Health, National Cancer Institute
R01 CA154596-01
“Smoking Response –Prevention Intervention for Cancer Patients”
Direct: $1,445,378 Total: $2,413,060
7/1/08-6/30/11 Florida Department of Health, Bankhead Coley
08KN-14
“Defining the Signaling Network of NRAS Mutated Melanomas”
Direct: $338,043 Total: $365,192
Publications:
Simmons, V.N., Litvin, E.B., Patel, R.D., Jacobsen, P.B., McCaffrey, J.C., Bepler, G., Quinn, G.P., & Brandon , T.H. (2009). Patient-provider communication and perspectives on smoking cessation and elapse in the oncology setting. Patient Education and Counseling, 77, 393-403.
Simmons, V.N., Litvin, E.B., Unrod, M., & Brandon, T.H. (in press). Oncology healthcare providers’ implementation of the 5 A’s model of brief intervention for smoking cessation: Patients’ perceptions.
Erin Siegel, PhD
2009
$41,666
Progress Report Summary
Project 1: DNA Methylation and HPV: Predicting Anal Cancer Treatment Response
Miles for Moffitt funds are currently being utilized to support a collaboration between Dr. Siegel and Dr. Shibata, MCC GI surgeon. The goals of this research are to investigate the association between DNA methylation, human papillomavirus and treatment response in anal cancer. As part of an NIH R01 grant resubmission, we conducted a pilot study in collaboration with the Radiation Therapy Oncology Group utilizing tissues archived within a completed clinical trial. Miles for Moffitt award funded this pilot study (see Expenses FY’2011). For our pilot study, we used 14 randomly selected patients with favorable 3-year Local regional response to the 5FU-Mitomycin C plus radiation treatment and 10 patients with unfavorable 3-year response. All cases were evaluated on the novel state of the art Illumina HumanMethylation27 Array. Methylation data were compared across groups. These data have been accepted as a Podium Presentation at the International Papillomavirus Meeting in Berlin, Germany (September, 2011).
Unfortunately, the re-submitted R01 did not get funded; however, we were able to secure funding from the American Society of Colon and Rectal Surgeons to continue this research. This ASCRS grant has limited funds per years ($50k) and Miles for Moffitt funds are needed to complete the proposed research. The combination of ASCRS Foundation funds and the Miles for Moffitt funding will enable us to generate strong data for publication and puts us in a very competitive position for NIH funding in 2012.
Project 2: Insulin- Like Growth Factor Axis and Colon Cancer Outcomes
The goals of the study are to establish a cohort of colorectal cancer patients with 12 months of follow-up and examine the association between biomarkers of the Insulin-like Growth Factor (IGF) pathway and colorectal tumor biology and patient quality of life. This study is establishing procedures of patient recruitment and synthesizing research within the Total Cancer Care (TCC) initiative at Moffitt. TCC is a large initiative that has established infrastructure for the recruitment of cancer patients across 21 sites across the US. TCC has set SOPs for patient recruitment, specimen collection and transfer of clinical data.
We are expanding recruitment to included four additional TCC clinical sites to increase patient accrual and expand diversity. New recruitment sites include St. Joes Candler (Savannah, Ga), St. Joes (St. Pete, Fl), Watson Clinic (Lakeland, Fl) and Sarasota Memorial (Sarasota, Fl). The additional recruitment sites will increase our sample size by ~75 participants and provide necessary feasibility data for NIH R01 grant application.
This study is currently funded through the Bankhead-Coley New Investigator award (July 2009 – June 2012). We are planning on requesting a no cost extension of this grant into 2013; however current funding will not fully support the recruitment at affiliate sites. We propose to utilize Miles for Moffitt Funds to establish and sustain the recruitment of patients at these four new clinical sites. This research activity will take place over the next two years
Grants:
9/29/09-8/31/11 National Institutes of Health, National Cancer Institute
R03 CA143980-01
“Defining Novel Biomarkers for Cervical Cancer Etiology and Progression by Quantitative Epigenomic Analysis”
Direct: $119,584 Total: $175,116
Publications:
Hernandez J, Elahi A, Siegel E, Coppola D, Riggs B, Shibata D. HPV L1-Capsid Protein Detection and Progression of Anal Squamous Neoplasia. Am J Clin Pathol. 2011 Mar;135(3):436-41. PMID: 21350099
Hernandez JM, Siegel EM, Elahi A, Eschrich SA, Coppola D, Riggs B, Grady WM, Giuliano AR, Shibata D. DNA Methylation Profiling Across the Spectrum of HPV-Associated Anal Squamous Neoplasia. (under revision PLoS ONE) 2011.
Juan Del Valle, PhD
2009
$41,666
Progress Report Summary
Funding from the Miles for Moffitt Award has been used in our lab to initiate a number of new projects in drug discovery. This allowed us to hire a postdoc who generated preliminary data ahead of two Florida grants obtained from the James & Esther King and Bankhead-Coley Programs. In addition, we currently have 2 NIH R21 grants pending (on inhibitors of Akt and siderocalin) that are focused on research emanating from the Milestone Award. Two manuscripts recently submitted for publication and are under review.
Grants:
7/1/10-6/30/12 Florida Department of Health, Bankhead Coley
1BN03
“Synthetic & Biologival Studeies of Marine-Derives Non-Ribosmoal Peptides”
Direct: $347,824 Total: $399,998
7/1/10-6/30/13 Florida Department of Health, Bankhead Coley
1KN03
“Natural Prodduce –Inspired Approached Targeting MCL-1”
Direct: $347,824 Total: $399,999
Yulia Nefedova, PhD
2009
$41,666
Progress Report Summary
The goal of our study was to investigate whether immature myeloid cells could affect multiple myeloma (MM) growth. Myeloid cells were isolated from bone marrow of control tumor-free mice or from bone marrow of MM tumor-bearing mice, mixed with MM cells and injected subcutaneously into flank of mice. Tumor size was measured daily. We found that tumors appeared and grew significantly faster in mice received myeloid cells isolated from tumor-bearing mice as compared to mice injected with myeloid cells from tumor-free mice. In parallel, we compared tumor growth in S100A9 knockout and wild-type mice and found that MM growth was substantially delayed in S100A9 knockout mice. Taken together, these data indicate that myeloid cells play a critical role in MM tumor growth. Currently, we are investigating mechanisms and therapeutic implications of this effect.
Grants:
3/1/11-2/28/13 Multiple Myeloma Research Foundation
“Regulation of Multiple Myeloma by Myeloid Cells”
Direct: $227,273 Total: $250,000
Publications: N/A