Liver / GI / GU includes research in the following areas:
Initiated in 2009, the Colorectal Research Program was developed with three main areas of focus:
Colorectal cancer is the third most common malignancy among both men and women in the United States and represents the second leading cause of cancer death. In addition to known genetic syndromes that increase risk of cancer, there are a variety of risk factors in the general population for developing colorectal cancer. These risk factors include consumption of red meat and especially processed meats, obesity, and a sedentary lifestyle.
The molecular pathways that transform a benign colorectal polyp into cancer may include genetic mutations and epigenetic phenomena that turn genes on and off. The colorectal cancer research program at HMRI currently focuses on the role of increased body mass index on epigenetic changes that occur in the colon.
By age 50, one half of women will develop clinical problems related to pelvic floor relaxation. While not life-threatening, these disorders which include incontinence, obstruction, pelvic organ prolapse, and pain have a significant impact on quality of life. These problems can cause progressive dysfunction, and by age 80, 11% of women in the United States will undergo surgery for incontinence or pelvic organ prolapse.
Our research program seeks to understand age-related changes in the pelvic floor with aging and obesity utilizing state-of-the-art MRI technology. Moreover, Dr. Kaufman was one of 16 international investigators who studied the effect of sacral nerve stimulation on bowel control. This therapy was recently approved by the FDA for the treatment of fecal incontinence and is currently available to patients at the Huntington Hospital. The pelvic floor research program is intimately related to our clinical efforts in the multidisciplinary treatment of pelvic floor disorders at the Huntington Hospital.
This program focuses upon improving outcomes in colorectal surgery patients. Our goal is not only to track the clinical outcomes of patients with colorectal disorders treated at the Huntington Hospital, but to utilize validated outcomes based databases towards understanding risk and improving care for patients undergoing surgery for colorectal diseases.
Chung DC. The genetic basis of colorectal cancer: insights into critical pathways of tumorigenesis. Gastroenterology. 2000 Sep;119(3):854-65.
Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci 1999;96(15):8681-6.
Wexner SD, Coller JA, Devroede G, Hull T, McCallum R, Chan M, Ayscue JM, Shobeiri AS, Margolin D, England M, Kaufman H, Snape WJ, Mutlu E, Chua H, Pettit P, Nagle D, Madoff RD, Lerew DR, Mellgren A. Sacral nerve stimulation for fecal incontinence: Results of a 120-patient prospective multi-center study. Ann Surg. 2010; 251:441-449.
The HMRI Liver Center’s clinical research programs are directly related to our customized patient-centered care and treatment. The HMRI Liver Center’s research focuses on the natural history and clinical course of viral and autoimmune diseases affecting the liver and has authored more than 230 peer-reviewed articles in these areas. Our participation in multi-centered clinical research trials using the most advanced drugs, allows us to deliver medical care on the cutting-edge of medical and pharmaceutical technologies. These multi-centered clinical trials have led to FDA approval of medications which have dramatically impacted the length and quality of life for patients living with chronic liver diseases.
The HMRI Liver Center hepatocellular research studies have elucidated the pathogenesis of chronic viral infections and the role it plays in the development of hepatocellular carcinoma (HCC). Together with leading clinicians and research collaboration with UCLA, the HMRI Liver Center utilizes medical treatments which have significantly prolonged the lives of patients with hepatobiliary malignancies. In addition, HMRI is continuing to search for liver cancer molecular markers which will enhance early detection and future treatment modalities for patients afflicted with this highly fatal cancer.
The Prostate Research Program and the Molecular Pathology Program have been evaluating the expression of functional androgen receptor (AR) as a potential prognostic biomarker for the development of castration resistant prostate cancer (CRPC). The presently available markers have not been shown to be effective in predicting the development of CRPC. The results have demonstrated the presence of functional AR in both primary cancer cells and metastatic cancer cells with significantly higher levels present in metastatic cancer cells. Cases that had undergone castration and hormone therapy still showed continued AR expression indicating that prior therapy did not prevent the development of castrate resistance. This has never been demonstrated in human tissue. According to publications, this has only been done in rodent models.
Zon, G., Barker, M.A., Kaur, P., Groshen, S., Jones, L.W., Imam, S.A., Boyd, V.L. Formamide as a Denaturant for Bisulfite Conversion of Genomic DNA: Bisulfite Sequencing of the GSTPi and RARb2 Genes of 43 Formalin-Fixed Paraffin-Embedded Prostate Cancer Specimens. Anal Biochem, 392(2):117-125 (2009). PMID: 19505431
Baisakhi, S., Arase, A., Imam, S.S., Tsao-Wei, D., Naritoku, W.Y., Groshen, S., Jones, L.W., Imam, S.A. Overexpression of E-Cadherin and ß-Cartenin Proteins in Metastatic Prostate Cancer Cells in Bone. Prostate. 68(1): 78-84 (2008). PMID: 18008331
Baisakhi, S., Kaur, P., Tsao-Wei, D., Naritoku, W.Y., Groshen, S., Datar, R.H., Jones, L.W., Imam, S.A. Unmethylated E-Cadherin Gene Expression is Significantly Associated with Metastatic Human Prostate Cancer Cells in Bone. Prostate. 68(15):1681-1688 (2008). PMID: 18712716
Our collaborative study with Dr. Lelund Chung and Dr. Haiyen Zhau from Cedars Sinai Medical Center was designed to test the hypothesis that novel, biologically relevant, noninvasive techniques of assessing changes in risk related metabolic products will improve risk assessment for treatment initiation versus continued surveillance for management of prostate cancer.
We reported that the activation of RANK and c-Met signaling components in both experimental mouse models and human prostate cancer (PC) specimens predicts bone metastatic potential and PC patient survival. In this study, we tested the hypothesis that a population of metastasis-initiating cells (MICs), known to express stronger RANKL, phosphorylated c-Met (p-c-Met), and neuropilin-1 (NPR1) signaling than bystander or dormant cells (DCs), can be detected in primary PC specimens and that the relative abundance of MICs compared to DCs could predict the survival of PC patients. We employed a multiplexed quantum-dot labeling protocol to detect the co-expression of RANK and c-Met signaling components at the single cell level. We observed PC cells with MIC and DC phenotypes in primary formalin fixed paraffin embedded (FFPE) PC tissue specimens and the relative abundance of MICs compared to DCs in primary PC correlated with PC patient survival.
Li, Qin, Li, Qua, Nuccio, J., Liu, C., Duan, P., Wang, R., Jones, L.W., Chung, L.W.K., Zhau, H.E. Metastasis Initiating Cells in Primary Prostate Cancer Tissues From Transurethral Resection of the Prostate (TURP) Predicts Castration-Resistant Progression and Survival of Prostate Cancer Patients. Prostate. 10.1002/pros 23011 (2015). PMID 25990623