Wake Forest Baptist Health internal medicine researchers and their teams will be recognized for their leading-edge roles in moving research into clinical practice at the department’s Top 2018 Research Papers event during Research Day on May 16. The following researchers and their teams were chosen:
Hariom Yadav, PhD, “Human-Origin Probiotic Cocktail Increases Short-Chain Fatty Acid Production via Modulation of Mice and Human Gut Microbiome.” Novel human probiotics from gastrointestinal tracts of infants have the capacity to modulate the gut microbiome. When given to mice, the probiotics increased the production of beneficial metabolites, such as short chain fatty acids (SCFAs). Because production of specific SCFAs, are significantly decreased in obesity, diabetes, aging, cancer, and other diseases, the use of human probiotics may prove to be a beneficial addition to the treatment of diseases that involve reduced SCFA production.
Leah Solberg Woods, PhD, “Genetic Fine-Mapping and Identification of Candidate Genes And Variants for Adiposity Traits in Outbred Rats.” The majority of genes contributing to obesity are unknown. We identified novel genes that play a role in susceptibility to obesity using a rat model. Future study of these genes will lead to a better understanding of the molecular mechanisms underlying obesity, potentially leading to novel therapeutic targets.
David P. Miller Jr., MD, “Effect of a Digital Health Intervention on Receipt of Colorectal Cancer Screening in Vulnerable Patients: A Randomized Controlled Trial.” An iPad application that informs patients of colorectal cancer screening and lets them order their own screening tests doubled the number of patients who completed screening. Half of patients ordered their own screening through the program.
David M. Herrington, MD, “Proteomic Architecture of Human Coronary and Aortic Atherosclerosis.” High-resolution mass spectrometric study of how proteins produced by genes interact and network analyses produced new insights and identified new protein biomarkers for premature atherosclerosis. High-throughput, multidimensional imaging will soon be available to support precision medicine treatment and prevention of atherosclerosis.
Barry I. Freedman, MD, “FGF23 Concentration and APOL1 Genotype Are Novel Predictors of Mortality in African Americans with Type 2 Diabetes.” The African American-Diabetes Heart Study contains among the most intensively phenotyped populations with type 2 diabetes. A phenotype describes a person’s characteristics and traits. Last year, the study assessed new predictors of mortality. An analysis identified higher fibroblast growth factor 23 (FGF23) concentration and absence of APOL1 renal-risk genotypes as the strongest predictors of mortality. Genotypes are the genes inherited from parents. These data add to growing evidence supporting associations of FGF23 with mortality. Mechanisms whereby these predictors impact survival remain to be determined.
Suzanne Craft, PhD, “A Nonhuman Primate Model of Early Alzheimer's Disease Pathologic Change: Implications for Disease Pathogenesis.” There is a great need for Alzheimer’s disease (AD) models that more closely replicate complex human disease. We documented naturally-occurring age-related AD pathology that was correlated with imaging, CSF, and behavioral characteristics that typify the early stages of AD. Future studies may use this and similar models of sporadic early AD to explore disease mechanisms, identify new biomarkers, and test novel therapeutic strategies.
Timothy S. Pardee, MD, “A Phase I Study of CPI-613 in Combination with High-Dose Cytarabine and Mitoxantrone for Relapsed or Refractory Acute Myeloid Leukemia. ”It is unclear what contributions metabolism makes to therapy resistance in acute myeloid leukemia (AML). We found AML cells upregulate mitochondrial metabolism in response to chemotherapy. The inhibition of mitochondrial metabolism, with CPI-613, increased sensitivity of AML cells to chemotherapy and showed promising results in a phase I trial in older adults and patients with poor-risk genetic changes. These data are the basis for a newly opened phase III clinical trial.
Dalane W. Kitzman, MD, “Regional Adipose Distribution and its Relationship to Exercise Intolerance in Older Obese Patients Who Have Heart Failure with Preserved Ejection Fraction.” Obese heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure in the U.S. However, its pathophysiology is not well understood, and the only proven treatments, both first described at Wake Forest Baptist, are exercise training and caloric restriction (JAMA 2016). In this study, we showed that the location of fatty tissue, specifically intra-abdominal, is an independent predictor of important outcomes, including impaired exercise capacity, above and beyond total fat mass. Our results were recently extended when MESA study investigators showed that intra-abdominal fat was a strong, independent predictor of development of HFpEF, and another study that showed that intra-abdominal fat, and the inflammatory immuno-regulatory proteins it elaborates, are independent predictors of death in HFpEF.
Deanna N. Jones, MD, “Frequency of Transition from Stage A to Stage B Heart Failure after Initiating Potentially Cardiotoxic Chemotherapy.” We found that among patients with Stage A heart failure, who were treated with potentially cardiotoxic chemotherapy, 19% moved to Stage B heart failure 3 months after starting chemotherapy. Furthermore, we found that their heart failure Stage 3 months after starting chemotherapy was predictive of future trajectory 6 to 24 months after initiating chemotherapy. About 80% of patients still classified in Stage A heart failure at 3 months remained in Stage A heart failure at 6 to 24 months post-treatment, and of those who transitioned to Stage B heart failure at 3 months, roughly 60% were still classified in Stage B heart failure at 6 to 24 months post-treatment
Timothy M. Hughes, PhD, “Arterial Stiffness and Dementia Pathology: Atherosclerosis Risk in Communities (ARIC)-PET Study.” Arterial stiffness, as measured by pulse wave velocity, is an emerging risk factor for dementia through its relationships with cognition, cerebral small vessel disease, β-amyloid deposition and neurodegeneration in areas prone to Alzheimer’s disease. In this manuscript, we replicate these associations in a diverse group to show that arterial stiffness is a generalizable risk factor for dementia-related pathology.
Michael V. Rocco, MD, “Effects of Intensive Blood Pressure Treatment on Acute Kidney Injury Events in the Systolic Blood Pressure Intervention Trial (SPRINT).” In the SPRINT trial, intensive control of systolic blood pressure to a level of 120 mm Hg resulted in about a 25% decrease in cardiovascular events and all cause death compared to a systolic blood pressure of 140 mm Hg (NEJM 2015). Although intensive blood pressure lowering resulted in more frequent episodes of acute kidney injury, most cases of acute kidney injury were mild and most participants had complete recovery of kidney function.