My research focuses on the impact of dietary carbohydrate quality on substrate utilization, body composition, insulin resistance, energy and glucose metabolism. We have used RCT incorporating indirect calorimetry, body composition techniques, stable isotopes and a dietary intervention. Prior NIH RCTs have involved glycemic index diet interventions in older adults and assessing energy expenditure during hemodialysis. Two current studies include use of a low glycemic, Mediterranean diet and exercise intervention in patients with pulmonary arterial hypertension to assess the effects on glucose metabolism, insulin resistance, and nitric oxide deficiency. A recently submitted grant focuses on these same components in obese pregnant women.
My general research theme focuses on the identification of new pathways and regulatory mechanisms, by associating metabolomics and stable isotope technologies as follows:
- Explore strategies to starve colon cancer cells by blocking glutamine utilization.
- Expand previous findings that explain the failure of liver transplantation in the treatment of propionic acidemia. ROI to be submitted July 2016.
- Expand previous work on the regulation of coenzyme A metabolism, in relation to inborn errors of metabolism. ROI to be submitted in October 2016.
Dr. Chance is noted for a long-standing research track record in quantitative mass spectrometry; Dr. Chance's laboratory invented mass spectrometry based protein footprinting, a well-known and popular quantitative proteomics technology for examining protein structure. Recently, his work combining proteomics, genomics, and bioinformatics, has provided novel approaches and biomarkers for understanding colon cancer and glioblastoma and identifying key pathways that mediate complications of HIV. He has a long-standing demonstrated experience developing complex, internationally recognized biomedical science projects and Centers, including developing and implementing technologically advanced experimental and computational infrastructure for biomedical research.
My current research projects include:
- Characterizing driver genes in cancer
- Exploring shared disease mechanisms associated with COPD and lung cancer.
- Integrating genomic analysis of cancers to identify pathways and classify tumors.
- Microbiome and related epigenetic alterations in head and neck squamous cell carcinoma.
- Classifying drugs by multiple genetic features to understand mechanisms of multidrug resistance and identify repositionable synergistic therapies.
- Identifying the role of epigenetic regulators in triple negative breast cancers.
- Developing software tools to analyze/improve our understanding and interpretability of proteomics and genomics datasets, and
- Predicting contagious disease diffusion using social media big data.
One of my long-term goals is to create a personalized/precision medicine paradigm for cancer treatment, where a patient's genome/proteome guides identification of the best treatment.
My research studies use emerging communications technologies to reduce obesity-related mortality and morbidity with an emphasis on cancer. He has expertise in the areas of technology development and the design, implementation, and analysis of behavioral interventions. My current research focuses on examining the relationship between social media use and physical activity and dietary behaviors through the analysis of nationally representative survey data and by conducting intervention research using social media as a means of increasing social support and behavioral modeling for optimal dietary and physical activity behavior.
My research focuses on the development of liver injury and disease as a consequence of obesity or alcohol consumption. We began by investigating the genetic susceptibility to liver injury using chromosomal substitution strains. Our research has led us into the world of immunology. Currently we are investigating 2 genes (NLR Family, CARD Domain Containing 4, NLRC4 and phosphoenolpyruvate carboxykinase, Pck l). We have developed a myeloid specific knockout of Pckl and are investigating the role of Pckl in the immune system for the development of liver injury and obesity.
My research interest is in computational/statistical biology with emphasis on developing data mining methods in high-dimensional data, mostly from high-throughput technologies. Recent focus has been in Bump Hunting problems in Classification, Regression and Survival settings with clinical applications in developing improved diagnostic and prognostic tools for personalized medicine. Other interests are in Bayesian Model Selection and Predictive Modeling as applied to Differential Expression, Genetic Association and Genetic Interaction problems; Regularization and Variance Stabilization of high-dimensional data; as well as Statistical Computing and Software Development.
My research includes study of the metabolic effects of antihypertensive and antidiabetic drugs and their mechanisms, the role of oxidative stress in the onset of Type 2 diabetes, and the cardiometabolic effects of commonly prescribed drugs, as based on electronic medical records.
My research interests have centered on the use of metabolomics and stable isotope techniques for new metabolite and pathway discovery and more recently expanded to include:
- Dietary supplement use, motivations for use and regulation.
- Education, knowledge, and attitudes of integrative medicine among dietetic educators, and
- Nutrition education for health care professionals.
My research is focused on the health consequences of energy imbalances [i.e., mismatch between energy intake (El) and energy expenditure (TEE)] in obesity (El>TEE) and in athletes with low energy availability (EA; EI<rEE). Specifically, I have examined dietary interventions (i.e., flavonoids or carbohydrate-protein supplementation) targeted at alleviating inflammation, oxidative stress, impaired menstrual and musculoskeletal health. Future research plans include:
- Identifying biomarker(s) for differential diagnosis of exercise-induced menstrual dysfunction.
- Examining flavonoid-rich food sources as "treatment" in energy imbalance.
- Characterizing health consequences of low EA in male athletes; and
- Validating user-friendly research tools for energy status (i.e., apps and fitness trackers).
Mary Beth Kavanagh
My current research projects include:
- A pilot study of a protein- sparing modified fast in obese endometrial cancer survivors, with the main outcomes of weight loss, changes in quality of life, changes in lipids, and biomarkers of inflammation.
- We have just completed a study "Adapting an Existing Cultural and Linguistic Competence Self-Assessment Tool for Dietetic Practice” in collaboration with the National Center for Cultural Competence at Georgetown University, manuscript in progress.
- Co-investigator on a study that is co-sponsored by the Academy of Nutrition and Dietetics and Gardens for Health International for a 14 week nutrition and agriculture education intervention for pregnant women in Rwanda who already have a severely malnourished child.
The Narla laboratory has developed a novel series of small molecular drug candidates (SMAPs) that activate the protein Serffhr phosphatase PP2A and simultaneously reduce both the MAPK and AKT effector pathways in lung cancer cell lines and mouse models of the disease. In collaboration with Dr. Narla, I have employed a novel MS-based protein footprinting approach along with photo-affinity labeling to confirm the drug binding site within the PP2A structural subunit A, and establish the specific mechanism of drug-dependent allosteric activation of PP2A. Currently, my research is focused on understanding the function deficit of specific PP2A mutations in cancer patients and on the development of a possible mass spectrometry-based assay for drug screening.
G protein coupled receptors (GPCRs) govern the regulation of many homeostatic processes including heart rate, blood pressure, glucose metabolism as well as the sensations of sight and smell. GPCRs are the largest class of small molecule therapeutics and as such an in depth understanding of their mechanism of activation is of broad interest. My laboratory attempts to answer these fundamental questions utilizing a combination of X-ray crystallography, mass spectrometry and computer modeling. A second research interest employs ultra-high resolution structures to answer fundamental questions about the catalytic mechanism of serine proteases and hydrolases.
My research projects include:
- Nutritional biochemistry, Redox biology, dietary antioxidants, mechanisms of action of the tocopherol transfer protein, non-alcoholic fatty liver disease, and
- Cancer biology. Cancer-related alterations in growth-factor signaling cascades; the roles of small GTPases in mitogenic and oncogenic signaling pathways, and cell motility, invasion and metastasis.
My laboratory is motivated to develop mass spectrometry methods for profiling proteomes, characterizing post translational protein modifications, and probing structural changes of proteins, applying the methods to answer specific biological questions. We are currently focused on:
- Developing a method to identify the targets of a drug, and
- Revealing how the proteome changes in C. e/egans during its development.
My area of research concentrates on the regulation of pathways of intermediary metabolism in whole body and organs systems. My research has emphasis on metabolic pathology of glucose and lipid metabolism such as with obesity, insulin resistance and brain reperfusion/oxidative injury. Current research projects involve the study of the effects of energy imbalance associated with cystic fibrosis (in skeletal muscle, adipose) and brain injury (related to aging, oxidative injury), as well as the use of dietary interventions to improve outcome and survival from these diseases. Stable isotopes and mass spectrometry together with targeted metabolomics and lipidomics are tools that I use to study the metabolic mechanisms associated with disease and pathology.
The main hurdle in macromolecular crystallography (MX) is obtaining large and well diffracting crystals. It will save weeks and maybe years of time if scientists can work with micron-sized crystals and still get quality diffraction data. Serial crystallography, where a full dataset is merged from hundreds or thousands of micron-sized crystals, has been developed with X Ray Free-Electron Laser. With the new bright synchrotron sources and micro-focusing MX beamlines, it is now possible to do serial crystallography at a conventional synchrotron beamline. In the next few days to months, I will be learning the experimental protocols and testing software in serial crystallography.
Nutritional status and hematology/anemia; absorption of minerals, including naturally occurring chelates and as food fortificants, especially iron, and metabolism; interplay between dietary iron and pathophysiology of clinically significant disorders/diseases, especially tumorigenesis.
My research is in the area of cancer molecular epidemiology. I am interested in the effects of both genetics and lifestyle on cancer risk, aggressiveness, progression and outcomes. My current focus areas include energetics/obesity/metabolic related traits, breast cancer and melanoma. I also have an active area of research in clinical biomarkers in cancer care.
Our laboratory is interested in delivering proteins into cells for research and therapeutic purposes. Leveraging our expertise in cellular susceptibility to HIV infection and identification of host factors that influence viral replication, we have developed a non- infectious nanoscale rQtein Qelivery (nanoPOD) platform to deliver proteins into the cytoplasm, nucleus, and intracellular organelles of cells. We are optimizing this platform in vitro and - with collaborators - are exploring its potential in vivo, including as a cancer immunotherapeutic and vaccine agent and as enzyme replacement therapy for congenital genetic deficiencies, emphasizing targeted protein delivery to specific tissues and cells in the body.
Our research is focused on basic and translational studies of estrogen receptor (ER), a key target of breast cancer therapeutics. Specifically, we focus on:
- Molecular biophysics of estrogen receptor, enabled by the power of integration of multiple biophysical techniques (e.g., small-angle scattering, hydroxyl radical footprinting, and energy-landscape simulation).
- Structure-based drug discovery by novel targeting of a new ER binding surface, and
- A long-neglected folding phenomena of an intrinsically disordered domain of the ER, a critical aspect of breast cancer activation.