Research by Specialization
VCU Medical Center is made up of faculty with a wide range of research interests. There is active intra-departmental as well as inter-departmental collaboration directed primarily by the mutual interest in a given disease process. To provide insight into the ongoing research in the department, we have categorized active research it under various research foci.
Below you will find some of our current research listed by specialization and research foci. Click on the researcher's name to go to their page in the VCU Faculty Expertise Directory.
Mechanistic Insights of Premature Ventricular Contractions-induced Cardiomyopathy
Project Number: 1R01HL139874-01
Premature heart beats, so called “PVCs”, are commonly seen in patients with heart failure. PVCs have been recognized to debilitate the heart and cause heart failure, called "PVC‐induced cardiomyopathy (CM)". This cardiomyopathy also carries significant financial burden in the care of our patients. We anticipate that this study will help us understand the mechanism of this heart condition, leading to better prevention and treatment of PVC-induced CM and identification of high-risk patients with significant impact in heart failure admission, mortality and healthcare spending.
ROS; Inflammation; and Cardioprotection in Type 2 Diabetes
Project Number: 5R01HL118808-05
Oxidative stress, endothelial dysfunction and inflammation are critical early cellular events that lead to the development of Type 2 diabetes which has serious consequences in the development of cardiovascular diseases with devastating outcomes such as coronary artery disease, myocardial infarction, hypertrophy, and heart failure. The project goal is to test a novel and innovative hypothesis that phosphodiesterase-5 inhibitors including sildenafil (Viagra) and tadalafil (Cialis) may have a positive role in halting inflammatin and damage to the diabetic heart following heart attack. We believe that our study will have an immediate impact in the development of novel cardioprotective strategies leading to long-term beneficial outcome in heart disease, especially in patients with Type 2 diabetes.
Relaxin Signaling in Post-MI Cardiac Inflammation; Adverse Remodeling and Failure
Project Number: 1R01HL142281-01A1
Acute myocardial infarction (AMI, heart attack), which occurs due to a sudden obstruction of blood flow in one or more coronary arteries (ischemia) resulting in cellular death, remains a major cause of heart failure (HF) and death worldwide. Recently, the role of recombinant human relaxin-2, possibly through activating its receptor RXFP1, in protection of the heart and other organs against ischemia has propositioned this signaling axis as a strong candidate for treatment of cardiovascular disease. In this application, we have proposed conceptually innovative studies that will characterize RXFP1 in the context of ischemic heart disease and delineate its role in inflammasome suppression leading to overall cardioprotection against ischemia, adverse remodeling and heart failure.
The Effects of Interleukin-1 Blockade On Exercise Capacity In Patients With Recently Decompensated Systolic Heart Failure
Project Number: 1R61HL139943-01
Heart failure is a leading cause of morbidity and mortality in the US. While numerous studies have identified inflammation as a risk factor for adverse outcomes in heart failure, there are currently no anti-inflammatory therapies with a documented benefit in heart failure patients. This application will evaluate the use of targeted Interleukin-1 blockade to improve aerobic exercise performance and reduce hospital readmission in patients recently admitted for acute decompensated heart failure.
Gastroenterology, Hepatology and Nutrition
Lipidomics based diagnostics for nonalcoholic steatohepatitis
Project Number: 5R01DK105961-04
There is a great clinical and public health need to develop a diagnostic method to allow "point-of-care" diagnosis of nonalcoholic steatohepatitis, assess its progression towards cirrhosis and to evaluate its response to various treatments. This proposal will meet this challenge by identification and validation of a diagnostic signature of NASH, disease progression and response to treatment using state of the art high throughput lipidomic analysis of plasma samples obtained at the time of a liver biopsy in subjects with NAFLD from the NIDDK NASH Clinical Research Network and from matched controls without NAFLD.
Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)
Project Number: 5U01DK061731-17
The NIDDK NASH Clinical Research Network is a consortium that will focus on conducting clinical trials and performing translational studies to objectively define outcomes and develop biomarkers for diagnosis, prognosis and response to treatment.
HBV HIV Coinfection Research Network
Project Number: 5R01DK094818-05
Despite effective ART that can suppress both HIV and HBV, HBV-related liver disease remains a significant comorbidity in this population. Little is known about the histologic spectrum of liver disease, the significance of complete vs. incomplete HBV suppression, the utility of novel virologic and serum markers of diseases verity, and the long term renal and bone effects of TDF-based therapy. This proposal will address these important questions and impact the science and health of those coinfected with HBVHIV.
Modulation of Gut-Brain Axis Using Fecal Microbiome Transplant Capsules in Cirrhosis
Project Number: 5R21TR002024-02
Patients with liver cirrhosis can develop brain problems called hepatic encephalopathy that can recur due to increases in bowel bacteria that may be harmful since they can weaken the intestinal barrier. Despite current treatments that can help improve these bowel bacteria, patient often develop repeated episodes that can result in lasting brain damage. We plan to study transplanting a healthy person's stool microbes through pills in patients with recurrences of hepatic encephalopathy to improve their overall bowel bacteria and intestinal barrier.
General Internal Medicine
Enhancing use of Hydroxyurea in Sickle Cell Disease using patient navigators
Project Number: 4R18HL112737-05
To overcome barriers to hydroxyurea (HU) among adults with sickle cell disease (SCD), the state of Virginia, including the Virginia Department of Health and two academic medical centers, plans a two- phase demonstration, first of improvement in the percentage of adults with SCD who are in SCD specialty care (Phase I), then of improvement in adherence to HU of eligible SCD adults (Phase II). This project will be critically important and impactful by demonstrating the feasibility of a statewide community-based strategy to assist vulnerable SCD adults in obtaining SCD specialty care and likely prolonging life, a model that other states could adopt.
Hematology, Oncology, and Palliative Care
DYRK1A signaling in control of cell growth, proliferation and DNA damage repair
Project Number: 5R01CA188571-04
Cell proliferation is controlled by the mechanisms that promote quiescence and senescence; deregulation of these processes leads to cancer. DYRK1A protein kinase is required for quiescence and senescence by promoting the functions of the retinoblastoma family of tumor suppressors. The mechanisms of functionand regulation of DYRK1A are poorly understood, therefore this grant proposes to elucidate the DYRK1A signaling pathway, which controls cell proliferation and could play a role in the pathogenesis of cancer.
The role of the MBD2-NURD complex in gamma-globin gene silencing
Project Number: 1R01DK115563-01A1
This project is aimed at alleviating the major public health problem posed by sickle cell anemia and β-Thalassemia through facilitating development of new safe and effective treatment. The fundamental epigenetic mechanisms under study controlled by the MBD2-NURD transcriptional protein complex also bear on hematologic malignancies and other cancers.
Targeting multiple myeloma with Smac-mimetics and HDAC inhibitors
Project Number: 5R01CA205607-04
Despite recent advances, multiple myeloma remains an incurable disease, and consequently, new and more effective treatment approaches are urgently needed. The purpose of this project is to develop a novel therapeutic strategy involving two new classes of agents (i.e., Smac-mimetics and histone deacetylase inhibitors) that target important genetically abnormal pathways in multiple myeloma, with the ultimate goal of developing a rational basis for a new therapy for refractory/relapsed multiple myeloma, a disease for which satisfactory treatment options are currently lacking.
NIH R01 Strategies for Persistent Agitated Delirium in Palliative Care
Delirium or altered mental state is a critical yet poorly understood and undertreated problem in patients with advanced cancer admitted for palliative care. This project will test the effect of novel combination therapies that include neuroleptics and benzodiazepine rotation on a score for delirium developed at VCU, the Richmond Agitation Sedation Score (RASS). Outcomes will also include caregiver comfort, delirium related stress in caregivers and nurses and symptom expression, along with molecular correlates that will be tested such as IL-6 and IL-8 for future predictive biomarkers.
DOD Pilot Grant - Role of C-Terminal Binding Protein as Oncogene and Therapeutic Target in Epithelial Ovarian Cancer
Ovarian cancer has lagged other cancers in the development of targeted therapy due to the lack of gene mutations that are required for efficacy of this newest class of anti-cancer agents. As such, chemotherapy remains the mainstay of ovarian cancer treatment. This work provides a new path forward for ovarian cancer, by defining a novel transcription factor target. CtBP, as key to progression of ovarian cancer. The work will test a novel chemical inhibitor of CtBP that has shown efficacy in colon and breast cancer, to determine if it will slow progression or eradicate ovarian cancer in a variety of mouse models of human ovarian cancer.
Extracellular vesicles in small cell lung cancer early detection
Project Number: 5U01CA213330-03
Lung cancer is the leading cause of cancer deaths worldwide, with a disappointing 15% overall 5-year survival rate. In particularly, Small Cell Lung Cancer (SCLC) represents a subtype of lung cancer that carries even worse statistics. Poor survival rates are likely due to late presentation of disease, lack of methods for early detection, and molecular heterogeneity. Circulating extracellular vesicles (EVs) have been identified as potential biomarkers in human disease. We propose a multidisciplinary approach that integrates sequencing technology and the development of a simple tethered Cationic Lipoplex Nanoparticle (tCLN) biochip in studying extracellular vesicles as biomarkers for early detection of SCLC.