CAREER DEVELOPMENT PLAN1.2.1 Proposed mentorsMentors proposed for the sickle cell scholar include a career mentor in sickle cell disease, as well as oneof several potential research/scientific mentors, corresponding to each of the three tracks of research thescholar might pursue: anti-sickling, structural biology and vascular biology research; genetic-based therapyresearch; and sickle cell symptom research. These three tracks in turn correspond to the foci of the threeresearch teams of the Virginia CSCC research program.Dr. Wally Smith will serve as career mentor. His qualifications are listed below (see 'mentoring record,qualifications').The potential scientific mentors for the sickle cell scholar's training program are drawn from variousdisciplines within the University, including the Departments of Medicinal Chemistry, Physiology, InternalMedicine (Hematology/Oncology and Quality Health Care), and Psychiatry. The faculty encompasses seniorscientists with extensive track records of research and training. This training will provide an extraordinaryopportunity to strengthen existing scientific interactions of these researchers under the umbrella of the CSCC.1.2.1.1 Anti-sickling, structural biology, and vascular biology researchJ.2.JJ.J A nti-sickling structural' bio/ogy -Dr. Donald A brah amA pioneer and professor at VCU in medicinal chemistry, Dr. Abraham's research focuses on structurebaseddrug design utilizing X-ray crystallography, molecular modeling, synthetic medicinal chemistry, andstructure function studies involving allosteric proteins. His significant scientific contributions involve structurebaseddrug design in the discovery of allosteric modulators of hemoglobin for treatment of Sickle Cell Anemia(4-HM and 5HMF), ischemic diseases or problems (cardiovascular, stroke, trauma, dialysis, and enhancingblood storage) and as radiation sensitizers for treatment of inoperable brain cancer (RSR-13). RSR-13represents the first example of a molecule that was designed, synthesized, tested for pharmacological activityand toxicity, and transferred to the Clinic for Phase I clinical trials, all within the same University. Two currentprojects are the following: (1) Design and Development of Allosteric Effectors of PK. The long-term goals ofthis project are to design, synthesize and discover human erythrocyte pyruvate kinase (R) effectors to unravelthe allosteric mechanism of action. (2) Rational Design of Novel Estrogen Receptor Antagonists. The majorgoals of this project are to discover and employ new R-PK allosteric effectors that will aid in unraveling theallosteric switch mechanism of Human R-PK enzyme, and the discovery of selective effectors, which maytranslate into treatments for hypoxic diseases.J. 2. J.J.2 A nfi-sick/ing Vascu/ar biology - Dr. fioland PiftmanRoland Pittman PhD is professor of physiology, emergency medicine and biomedical engineering in VCU'sSchool of Medicine. He is a pioneer in the study of microcirculation, and has helped develop many techniqueswhich are considered the gold standard in assessment of oxygen transport. He is well-funded from the NationalInstitutes of Health to study how oxygen is transported by the tiniest blood vessels during severe hemorrhageand resuscitation. Using recently developed optical and electronic techniques, Dr. Pittman can determine therate at which oxygen moves through the microcirculation and from blood to tissue. He is currently studying thevarious geometric and hemodynamic factors that determine oxygen exchange in striated muscle. Currentexperimental studies utilize intravital video microscopy and computerized image analysis to obtain the pertinentgeometric, hemodynamic and oxygenation data from vascular networks composed of arterioles, capillaries andvenules. Studies on the diffusion of oxygen through muscle, using oxygen-sensitive electrodes, have led to areexamination of the intracellular pathway for oxygen. He is also developing an optical technique that alsomeasures nitric oxide at different points in the microcirculatory system.Dr. Pittman's understanding of the mechanisms of microcirculation, oxygen delivery, and microshock make hima unique resource to mentoring scholars studying sickle cell disease.1.2.1.2 Genetic sickle cell therapy research-Dr. Gordon GinderDr. Gordon Ginder is actively engaged in basic research into gene regulation and chromatin structure,which has been continuously funded by the NIH since 1980. He currently has two R01 grants that support hisresearch on the mechanisms by which DNA methylation and histone acetylation control gene transcriptionduring erythroid cell differentiation and in oncogenesis as well as a project aimed at dissecting the mechanismof HLA class I gene regulation in human tumor cells.1.2.1.3 Sickle cell symptom therapy research Dr. Wally R. SmithWally R. Smith, MD, the PI of the Virginia CSCC, is Professor and Chairman of the Division of QualityHealth Care at Virginia Commonwealth University. He is a sickle cell disease caregiver and a health servicesresearcher. He has served as an investigator on more than 35 externally funded grants and contracts,including principal investigator on over 10 federally or foundation-funded grants. He was an investigator in theCooperative Study of Sickle Cell Disease, and in the Multicenter Study of Hydroxyurea in Sickle Cell Anemia.He was Principal Investigator for the NHLBI-funded Pain in Sickle Cell Epidemiology Study, a prospectivecohort study of adults in Virginia with SCO. PISCES intensively studied detailed accounts of each of itssubjects' pain and response to pain, by collecting daily pain diaries for up to 6 months.Dr. Smith is now VCU site Principal Investigator for the NHLBI-funded Sickle Cell Disease ClinicalResearch Network, which involves eight sites nationally, enrolling patients into phase III clinical trials of sicklecell disease.Dr. Smith is also the PI of VCU's NHLBI-funded Sickle Cell Outcomes Research Core. In addition to theClinical Trials Network Award, VCU also simultaneously competed successfully to receive an NIH Sickle CellDisease Outcomes Research Core Award. The Outcomes Core is one of only two awarded nationally. It isfocusing on Behavioral epidemiology and Substance Use research in sickle cell disease. VCU was the onlySCO CRN site to receive both the Clinical Network and Outcomes Research Center awards.Dr. Smith also serves as Chairman of the Advisory Board for the NIH Sickle Cell Disease Health RelatedQuality of Life instrument development project. This two year project involves NIH project officers, theAmerican Institutes of Research, Oakland Children's Hospital researchers, patient advocates, and researchsubjects (physicians and patients) from around the US; in a project to best capture health related quality of lifeconcepts and measures specific to sickle cell patients. This measure is projected by be ready by 2008, and inthe RFA for the CSCCs is mentioned as one measure to be available for use by researchers in the CSCCs.1.2.1.4 Sickle cell symptom research Dr. Elinore McCance-KatzElinore McCance-Katz, M.D., Ph.D. in the Division of Addiction Psychiatry is a widely known addictionpsychiatrist with active research programs in pharmacotherapy of addictions, treatment of HIV/AIDS insubstance abusers and clinical pharmacology of drugs of abuse. Her expertise is in pain and addictionsassessment, research study design, and implementation in the area of addiction medicine and addictionpsychiatry.For the past two years, Dr. McCance-Katz and the Virginia CSCC symptom therapy research team havebeen exploring a number of important symptoms and syndromes experienced by patients with sickle celldisease. Collaborations to this point include the study of chronic pain and opiate use and abuse in sickle celldisease. She has provided addiction expertise in terms of study design and selection of survey instruments, aswell as participant assessment and data collection. As well, she has served as psychiatric and addictionmedicine evaluator in relevant proposed research studies in the SCO CRN and CSCC. Her laboratorycapability is part of the symptom therapy research team, and includes human laboratory studies aimed atbetter understanding the effects of opioid medications in patients with sickle cell disease including subjective,analgesic, cognitive, cardiovascular responses. She also has studied pharmacokinetics of opioids in thispatient population. Her human subjects laboratory will be available to sickle cell scholars for these and othersymptom-based studies. Her current collaborations within the Sickle Cell Disease Outcomes Research Centerare already yielding useful new information regarding opioid and substance use in sickle cell disease.Dr. McCance-Katz has also served as co-mentor for Dr. Imoigele Aisiku, one of the CSCC investigators.Their collaboration has led to an R-21 application on developing measures of addiction and substance use/abuse among sickle cell patients, included in this application. She is an experienced mentor, having trainednumerous MD and PhD trainees.
Showing the most recent 10 out of 23 publications
