FA 5 Progress Report WV-INBRE - Joan C. Edwards School of ...

FA 5 Progress Report WV-INBRE - Joan C. Edwards School of ... FA 5 Progress Report WV-INBRE - Joan C. Edwards School of ...

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Program Director/Principal Investigator (Last, First, Middle): Rankin, Gary O 123genital tract during Chlamydia infection in the mouse model. Preliminary data of the cervical regions of micerepresenting stressed and non-stressed mice showed no significant difference of hispathology. However,gross examination revealed that stressed and infected mice had fluid-filled and heavily extended uterusunlike non-stressed infected mice.Lastly, Dr. Belay is working to elucidate the mechanism(s) by which stress increases susceptibility toChlamydia trachomatis genital infection in the mouse model. Work is just beginning in this area.ARRA Supplement 3P20RR016477-09S2: Dr. Nalini Satanam, Project Director, MU, “Epicardial fatbiomarkers in patients with coronary artery disease in Appalachia”The immediate goal of this project is to identify unique fat biomarkers in epicardial fat obtained from WestVirginia patients with and without coronary artery disease (CAD) undergoing thoracic surgery. To date, withthe help of Dr. Christopher Adams, Dr. Paulette Wehner and Dr. Todd Gress (Dept. Cardiovascular Services)and Dr. Chowdhury (Dept. Thoracic Surgery) 60 subjects (30 men and 30 women) undergoing coronaryartery bypass graft surgery (CABG) at the St. Mary’s Heart Center, Huntington, WV (IRB approved study)have successfully recruited. They are in the process of recruiting control patients (no coronary arterydisease) undergoing valve type surgery. Blood, epicardial/perivascular fat and subcutaneous fat from allsubjects have been collected at the time of the surgery. The multiplex analysis (39 chemokines/cytokinearray) of the plasma samples obtained from CAD patients revealed that several cytokines/chemokineswere altered in a sex specific manner. Clinical correlations revealed a positive association with the increasein chemokines to increased presence of congestive heart failure. As a preliminary study, the human miRNAmicroarray consisting of over 88 miRNAs relevant to humans was performed on the RNA isolated fromepicardial fat and subcutaneous fat obtained from patients (n=8/sex). Females had no up-regulatedexpression while males had 27 up-regulated miRNAs in EF. Females had 13 while males had 16down-regulated miRNAs. MiR 122, MiR 196-b, MiR 302c, and MiR 210 all showed decreased expression inboth males and females and remains a cause for further study.Whole genome miRNA arrays (800 miRNAs inhumans) have been performed in approximately 8 patients. miRNAs were isolated from both epicardial andsubcutaneous fat and whole genome miRNA was performed using the Roche 480 system. Dataanalysis will be performed with the assistance of the Bioinformatics Core. Since the last APR fivepresentations have been made. Dr. Christopher Adams won the “Best Poster” at the WV Chapter of theAmerican College of Cardiology meeting and was selected to present the poster at the national meeting.One cardiology fellow (Dr. Adams), one medical student and six undergraduates have participated in thisresearch.ARRA Supplement 3P20RR016477-09S3 and HSTA initiativesThe goal of this supplement is to provide PUI undergraduates the opportunity to work on WV-INBRE fundedresearch projects and provide HSTA high school science teachers the opportunity to participate in thesummer research program to gain skills and experience in biomedical research. During the 2010-2011academic year, 8 undergraduates were placed in the WV-INBRE funded research labs at Bluefield StateCollege (2), Concord University (1), West Virginia State University (1), West Liberty University (2), andWest Virginia Wesleyan College (2) with S3. Five high school science teachers were funded from the S3supplement for 9-week summer research internships that began on June 13, 2011. Wendy Lee fromMusselman High School and Denise Gipson from Jefferson High School were mentored by Dr. Seung-yunKim at Shepherd University. Timothy Clifton from Herbert Hoover High School and Tiffani Smith fromHuntington High School were mentored by Dr. Robert Harris at West Virginia State University. ReneNorman from Sissonville High School was mentored by Dr. Dean Reardon at University of Charleston.Two additional teachers were funded from the prime award for internships this summer: Johnathan Baldwinfrom Scott High School was mentored by Dr. Gerald Hankins at West Virginia State University and BrianMcNeel from Cabell Midland High School was mentored by Dr. Richard Egleton at MU. During the2011-2012 academic year, 2 undergraduates were placed in the WV-INBRE funded research labs:Bluefield State College (1) and West Liberty University (1).PHS 2590 (Rev. 06/09)Continuation Format Page

Program Director/Principal Investigator (Last, First, Middle): Rankin, Gary O 124Other WV-INBRE - HSTA activitiesHSTA coordinator (Valerie Watson) and four other WV-INBRE AC representatives spoke at a number ofHSTA symposia during April-May 2011. Talks were given at the following symposia: Braxton/Webstercounties, Marion/Monongalia counties, Tucker/Barbour counties, Taylor County, Preston County,Greenbrier/Fayette counties, Eastern Panhandle Region, and Kanawha County. WV-INBRErepresentatives also acted as judges for the science projects. During the month of July, 2011, the followingWV-INBRE representatives participated in HSTA Summer Institutes at WVU, MU, and West Virginia StateUniversity: Ashley Gerard, Dr. Gerald Hankins and Dr. Robert Harris of West Virginia State University, Dr.Elsa Mangiarua of MU, and Valerie Watson, and 2011 INBRE summer interns: John Baldwin, HannahCavender, Timothy Clifton, Carissa Dunn, Ryan Johnson, Brian McNeel, Tiffani Smith and John PhillipThomas. INBRE/HSTA task force group was created in March 2011 and meets on a monthly basis duringthe academic school year to better coordinate the initiatives of INBRE and HSTA programs. INBREmembers include: Dr. James Sheil, Valerie Watson, Vickie Sanders, Dr. Elsa Mangiarua, Dr. AndrewShiemke, Jim Denvir and HSTA members include: Dr. Ann Chester, Kas Kasten, Cathy Morton-McSwain,Sara Hanks, Merge McMillion, and Summer Kuhn .ARRA Supplement 3P20RR016477-09S4, Dr. Monica Valentovic, Project Director, MU, “Resveratrolmodulates cisplatin oxidative stress”The goals of this translational project are to further explore the protective effects of resveratrol (RES)against cisplatin-induced nephrotoxicity and establish the mechanism for RES attenuation of cisplatin renaltoxicity. Dr. Valentovic has established a collaboration with Dr. Tim Troyer in the Department of Chemistry atWest Virginia Wesleyan University; who is collaborating with us on analysis of Pt for cisplatinpharmacokinetic studies, and a collaboration with Dr. Elaine Hardman, MU. The focus of the collaborationwith Dr. Hardman examines potential cancer chemo preventative effects of resveratrol when combined withcisplatin on breast cancer and is research that is translational. Since the last APR, five abstracts are eitherpublished or in press, along with one book chapter in press.In vitro renal studies: Initial studies were conducted using in vitro exposure of renal cortical slices toresveratrol (RES) and cisplatin. Cisplatin renal toxicity was evident as indicated by an increase in Lactatedehydrogenase (LDH) leakage within 120 min exposure. RES totally prevents LDH leakage by cisplatin andestablishes that RES prevents cisplatin renal cytotoxicity. RES does prevent cisplatin mediated depletion ofManganese Superoxide Dismutase (MnSOD) activity. Maintenance of Mn SOD by RES would allow forcontinued detoxification of superoxide anions (O2-) and diminished oxidative stress that is associated withcisplatin exposure of renal tissue. New methods were established in Dr. Valentovic’s laboratory to examineCu-Zn SOD and catalase enzyme activity. The results from her studies show that catalase enzyme activityis diminished by cisplatin. However, renal tissue in the presence of RES exposure to cisplatin did notdemonstrate as extensive a decline in catalase activity. She has also found that RES decreases oxidativestress by cisplatin by maintaining a more favorable balance between MnSOD and catalase. She has alsoshown that depletion of glutathione by cisplatin is not prevented by RES. Initial studies examiningmitochondrial swelling also suggest that RES does not act by preventing mitochondrial swelling induced bycisplatin. A time dependent study has shown extensive modulation by RES of oxidative stress induced bycisplatin. RES prevents cisplatin oxidative stress 60 min prior to induction of LDH leakage. These studiessuggest a RES greatly diminishes oxidative stress. More importantly, the decline in oxidative stress occursprior to LDH leakage.Pharmacokinetic studies: RES may reduce cisplatin renal toxicity by: a) increasing cisplatin renal clearanceor b) diminishing cisplatin renal tissue accumulation. Experiments have been completed to evaluate thepharmacokinetic interaction of RES and cisplatin. Male F344 rats were placed in metabolism cages.Parameters evaluated in metabolism cages include food and water intake, body weight, urine volume andurine protein. Rats were randomly divided into the following groups: Vehicle (DMSO and water), RES,Cisplatin (5 mg/kg, ip) and RES+Cisplatin. RES was injected 30 min prior to cisplatin. Plasma and renaltissue was collected 6, 24, 48 and 72 h after cisplatin injection. Urine was collected on ice for Pt analysis atthe following time points: 0-6 h, 6-24 h, 24-48 h. Pt is analyzed instead of cisplatin for all publishedPHS 2590 (Rev. 06/09)Continuation Format Page

Program Director/Principal Investigator (Last, First, Middle): Rankin, Gary O 123genital tract during Chlamydia infection in the mouse model. Preliminary data <strong>of</strong> the cervical regions <strong>of</strong> micerepresenting stressed and non-stressed mice showed no significant difference <strong>of</strong> hispathology. However,gross examination revealed that stressed and infected mice had fluid-filled and heavily extended uterusunlike non-stressed infected mice.Lastly, Dr. Belay is working to elucidate the mechanism(s) by which stress increases susceptibility toChlamydia trachomatis genital infection in the mouse model. Work is just beginning in this area.ARRA Supplement 3P20RR016477-09S2: Dr. Nalini Satanam, Project Director, MU, “Epicardial fatbiomarkers in patients with coronary artery disease in Appalachia”The immediate goal <strong>of</strong> this project is to identify unique fat biomarkers in epicardial fat obtained from WestVirginia patients with and without coronary artery disease (CAD) undergoing thoracic surgery. To date, withthe help <strong>of</strong> Dr. Christopher Adams, Dr. Paulette Wehner and Dr. Todd Gress (Dept. Cardiovascular Services)and Dr. Chowdhury (Dept. Thoracic Surgery) 60 subjects (30 men and 30 women) undergoing coronaryartery bypass graft surgery (CABG) at the St. Mary’s Heart Center, Huntington, <strong>WV</strong> (IRB approved study)have successfully recruited. They are in the process <strong>of</strong> recruiting control patients (no coronary arterydisease) undergoing valve type surgery. Blood, epicardial/perivascular fat and subcutaneous fat from allsubjects have been collected at the time <strong>of</strong> the surgery. The multiplex analysis (39 chemokines/cytokinearray) <strong>of</strong> the plasma samples obtained from CAD patients revealed that several cytokines/chemokineswere altered in a sex specific manner. Clinical correlations revealed a positive association with the increasein chemokines to increased presence <strong>of</strong> congestive heart failure. As a preliminary study, the human miRNAmicroarray consisting <strong>of</strong> over 88 miRNAs relevant to humans was performed on the RNA isolated fromepicardial fat and subcutaneous fat obtained from patients (n=8/sex). Females had no up-regulatedexpression while males had 27 up-regulated miRNAs in EF. Females had 13 while males had 16down-regulated miRNAs. MiR 122, MiR 196-b, MiR 302c, and MiR 210 all showed decreased expression inboth males and females and remains a cause for further study.Whole genome miRNA arrays (800 miRNAs inhumans) have been performed in approximately 8 patients. miRNAs were isolated from both epicardial andsubcutaneous fat and whole genome miRNA was performed using the Roche 480 system. Dataanalysis will be performed with the assistance <strong>of</strong> the Bioinformatics Core. Since the last APR fivepresentations have been made. Dr. Christopher Adams won the “Best Poster” at the <strong>WV</strong> Chapter <strong>of</strong> theAmerican College <strong>of</strong> Cardiology meeting and was selected to present the poster at the national meeting.One cardiology fellow (Dr. Adams), one medical student and six undergraduates have participated in thisresearch.ARRA Supplement 3P20RR016477-09S3 and HSTA initiativesThe goal <strong>of</strong> this supplement is to provide PUI undergraduates the opportunity to work on <strong>WV</strong>-<strong>INBRE</strong> fundedresearch projects and provide HSTA high school science teachers the opportunity to participate in thesummer research program to gain skills and experience in biomedical research. During the 2010-2011academic year, 8 undergraduates were placed in the <strong>WV</strong>-<strong>INBRE</strong> funded research labs at Bluefield StateCollege (2), Concord University (1), West Virginia State University (1), West Liberty University (2), andWest Virginia Wesleyan College (2) with S3. Five high school science teachers were funded from the S3supplement for 9-week summer research internships that began on June 13, 2011. Wendy Lee fromMusselman High <strong>School</strong> and Denise Gipson from Jefferson High <strong>School</strong> were mentored by Dr. Seung-yunKim at Shepherd University. Timothy Clifton from Herbert Hoover High <strong>School</strong> and Tiffani Smith fromHuntington High <strong>School</strong> were mentored by Dr. Robert Harris at West Virginia State University. ReneNorman from Sissonville High <strong>School</strong> was mentored by Dr. Dean Reardon at University <strong>of</strong> Charleston.Two additional teachers were funded from the prime award for internships this summer: Johnathan Baldwinfrom Scott High <strong>School</strong> was mentored by Dr. Gerald Hankins at West Virginia State University and BrianMcNeel from Cabell Midland High <strong>School</strong> was mentored by Dr. Richard Egleton at MU. During the2011-2012 academic year, 2 undergraduates were placed in the <strong>WV</strong>-<strong>INBRE</strong> funded research labs:Bluefield State College (1) and West Liberty University (1).PHS 2590 (Rev. 06/09)Continuation Format Page

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