Colleagues: Recently Tenured

KENNETH D. ALDAPE, M.D., NCI-CCR

Senior Investigator and Chief, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute

Education: Stanford University, Palo Alto, California (B.A.S., philosophy and biology); University of California at San Francisco (UCSF), San Francisco (M.D.)

Training: Residency and chief residency in anatomic pathology, UCSF; research fellowship, neuro-oncology, Preuss Laboratory for Molecular Neuro-Oncology, San Francisco; clinical fellowship, neuropathology, UCSF

Before coming to NIH: Faculty positions at MD Anderson Cancer Center, University of Texas (Houston), including chair and medical director, Department of Pathology (2001–2014); director, MacFeeters-Hamilton Brain Tumor Centre, and senior scientist, Princess Margaret Cancer Centre (Toronto, 2014–2018); associate member and director, Translational Genomics Laboratory, Ontario Institute for Cancer Research (Toronto, 2015–2018)

Came to NIH: in February 2018

Selected professional activities: Executive editor, Neuro-Oncology; international editor, Brain Tumor Pathology; on editorial review boards for several journals

Website: https://irp.nih.gov/pi/kenneth-aldape

Research interests: As a diagnostic and molecular neuropathologist, I focus on the genomics and molecular pathogenesis of primary brain tumors. I also work on the integration of new genomic and computational approaches to improve how cancer can be classified and treated. Cancer classification and treatment decisions will increasingly integrate these tools into clinical practice, and my vision is to contribute to this new paradigm in pathology.

In particular, my laboratory studies genomic and epigenomic alterations in brain tumors including glioma and meningioma. We characterize the biology of specific genomic alterations and how alterations contribute to the molecular pathogenesis and treatment resistance of aggressive brain tumors. We also use genomic signatures to identify clinically relevant subclasses. We hope that biologically based classification of brain tumors will lead to a greater understanding of why specific tumor subtypes may be more or less sensitive than average to therapeutics.

At the branch level, and as a diagnostic pathologist, I am passionate about the use of new technologies to improve how cancer is diagnosed. Although a light microscope is an effective tool for classifying most tumors, it’s not very helpful when it comes to diagnosing ambiguous or difficult cases. The use of genomic, epigenomic, and computational modalities shows promise for improving the precision and accuracy of cancer diagnostics. The future of diagnostic pathology will increasingly rely on genetic and epigenomic alterations as well as on computational and image-analysis approaches to define and classify cancer. I hope to promote precision diagnostics of cancer by integrating these approaches and other technologies with our current standard of care.

KONG CHEN, PH.D., NIDDK

Senior Investigator, Diabetes, Endocrinology, and Obesity Branch; Director, Human Energy and Body Weight Regulation Core; chief, Metabolic Research Section, National Institute of Diabetes and Digestive and Kidney Diseases

Education: Tennessee Technological University, Cookeville, Tennessee (B.S. in mechanical engineering); Vanderbilt University, Nashville, Tennessee (Ph.D. in biomedical engineering; M.S. in clinical investigation)

Before coming to NIH: Assistant professor of medicine (primary), biomedical engineering, and surgery at Vanderbilt University

Came to NIH: In 2006

Selected professional activities: Associate editor of European Journal of Clinical Nutrition and of Journal of Diabetes Science and Technology; member of Organizing Committees, International Conferences on Recent Advances and Controversies in Measuring Energy Metabolism and Body Sensor Networks Annual Conferences

Outside interests: Used to dabble in oil painting, water colors, and pencil and charcoal drawings, now mainly admires them in the museums; taking photos of wildlife, architecture, and unique cultures when he travels; reading; cooking; playing sports

Website: https://irp.nih.gov/pi/kong-chen

Research interests: I am interested in understanding how energy metabolism and physical activity are regulated. Ultimately, my lab’s goals are to develop safe and effective strategies for treating and preventing obesity in general populations and managing nutritional needs in patients with metabolic disorders.

As a biomedical engineer, I have designed and used whole-room indirect calorimeters (also called metabolic chambers) for measuring energy expenditure in people. I also do studies using wearable sensors for measuring people’s physical activity, sedentary behavior, and sleep (in the lab and at home). As a clinical investigator, I focus on cold-induced thermogenesis, brown adipose tissue, muscle activities, heart rate and heart-rate variability, and body and skin temperature in response to subtle changes in environmental temperature. We are quantifying the capacity of cold-induced thermogenesis (how many extra calories are burned during tolerable cold exposures) to see what the differences are between lean and obese subjects, men and women, and young and old, and among different races. We are also quantifying, in humans, the amount, activity, and distribution of brown adipose tissue, which will allow us to better understand how it regulates body temperature and metabolism.

Our three custom-made metabolic chambers measure minute-by-minute energy expenditure for several hours to several days. In this well-controlled environment, we can also simultaneously measure movement and physiological parameters to determine the impacts of physical activity, diet, medications, and other stimuli on energy metabolism, heart rate, and hormonal responses. In addition, we can use a variety of techniques to quantify people’s body composition.

Currently, we are working with intramural and extramural investigators to study energy balance in different populations such as people with diabetes, lipodystrophy, nonalcoholic fatty liver disease, inborn errors in metabolism, overgrowth, chronic fatigue syndrome, and certain cancers, as well as in a range of healthy volunteers (different ages and weights and in different geographic locations). We are also studying the effects of medications and dietary interventions on metabolism.

YAMINI DALAL, PH.D., NCI-CCR

Senior Investigator and Group Director, Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute

Education: St. Xavier’s College, Mumbai, India (B.Sc. in biochemistry and life sciences); Purdue University, West Lafayette, Indiana (Ph.D. in cell and molecular biology)

Training: Postdoctoral fellow at Fred Hutchinson Cancer Research Center, Seattle

Before coming to NIH: Postdoctoral research associate, Fred Hutchinson Cancer Research Center, Seattle

Came to NIH: In September 2008

Selected professional activities: Affiliate professor, Department of Biological Sciences, University of Maryland (College Park, Maryland); Faculty of 1000 since 2010; editorial boards for Public Library of Science, F1000 Research, Chromosoma, and Scientific Reports

Outside interests: Reading historical fiction, science fiction, and popular science; appreciating archaeology and ancient languages; enjoying folk and Americana music; biking; hiking; spending time with family and friends

Website: https://irp.nih.gov/pi/yamini-dalal

Research interests: My research focuses on centromeres, which are essential for chromosome segregation during cell division. My lab studies proteins called histones, the main protein components of chromatin (made up of DNA and protein), which packages and orders DNA into nucleosomes (the building blocks that make up chromosomes). In cancer cells, certain chromatin regions are fragile and prone to chromosomal rearrangements. We use an interdisciplinary approach—combining chromatin biochemistry, computational modeling, single-molecule microscopy, genetics, genomics, and cell biology—to determine how specialized chromatin structures contribute mechanically and epigenetically to centromere function.

The principle challenges we have addressed in recent years are how the essential centromeric histone variant called centromere protein (CENP) A (CENP-A) determines where the centromere is in located every cell cycle; whether CENP-A and its complexes physically alter the chromatin fiber to support the mechanical stresses of mitosis; and whether such states can be inherited over several cell cycles.

In previous work, we documented that CENP-A nucleosomal and pre-soluble assembly structures are diverse and possess unique modifications and dynamics that make them intrinsically distinct from histone H3 (one of the five main histones involved in chromatin structure).

In a recent breakthrough, we used an adaptation of a very-high-resolution microscopy technique, called atomic force microscopy, to make nanoscale elasticity measurements of CENP-A nucleosomes and compare them with nucleosomes that have different histone compositions. We found that CENP-A nucleosomes were surprisingly elastic, or “squishy,” but adding kinetochore proteins made them rigid. (Kinetochores are where the microtubules attach during cell division.) Overexpression of CENP-C in human cells showed that a higher CENP-C/CENP-A ratio decreases the elasticity of the nucleosome and “closes” the chromatin fiber.

We speculate that the plasticity of CENP-A might be the key inherited feature conserved across the CENP-A of all species, and it is this feature that is uniquely recognized by centromere-binding proteins.

In our second project, we are focusing on the regulation and deposition of histone variants in normal and cancer cells. We were the first to report that in embryonic stem cells, naturally excess CENP-A is involved in chromatin repair and that error-free CENP-A assembly to human centromeres requires targeted and cell-cycle specific transcription.

We were also the first to demonstrate that in human colon-cancer cell lines and tumors, CENP-A invades transcriptionally coupled H3.3 (a histone variant that is structurally much like histone H3) pathways to deposit hybrid CENP-A:H3 nucleosomes at non-centromeric regions.

A significant question remains: How does non-centromeric CENP-A drive cancer progression? In recent work, we have shown that CENP-A can drive chromosome instability by seeding large fragile domains outside of native centromeres. We have proposed that targeting cancer-specific CENP-A mis-interactions can potentially serve as a therapeutic target. To test these ideas, we have worked on H3.3 pathways that are invaded by CENP-A, and recently we developed high-precision computational-prediction approaches to block these interactions.

[RESEARCH SECTION WRITTEN BY MOHOR SENGUPTA, NEI]

PAULINE MENDOLA, PH.D., NICHD

Senior Investigator, Epidemiology Branch, Division of Intramural Population Health Research, National Institute of Child Health and Human Development

Education: State University of New York at Buffalo, Buffalo, New York (B.A. in social sciences interdisciplinary program; M.S. in epidemiology, social and preventive medicine; Ph.D. in epidemiology and community health)

Before coming to NIH: Chief of the Infant, Child, and Women's Health Statistics Branch, National Center for Health Statistics, Centers for Disease Control and Prevention (Hyattsville, Maryland, 2007–2011); health scientist and chief of the Epidemiology and Biomarkers Branch, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency (Chapel Hill, North Carolina, 1997–2007)

Came to NIH: In 2011

Selected professional activities: President, American College of Epidemiology; associate editor, Fertility and Sterility; recipient of the President’s Award from the Society for Pediatric and Perinatal Epidemiology

Outside interests: Enjoys spending time with her husband; visiting the amazing art galleries in the area; creating great meals to share with family and friends

Website: https://irp.nih.gov/pi/pauline-mendola

Research interests: Maternal asthma is the most common chronic disease in pregnancy. The burden of maternal chronic disease is high and continues to increase as advanced maternal age and overweight become more prevalent. My research is focused on the interplay of immune function (asthma, allergy, and maternal-fetal tolerance), oxidative stress, and air pollution in relation to preterm delivery, restriction of fetal growth, and other complications of pregnancy.

I am the principal investigator of the B-WELL-Mom study (Breathe- Wellbeing, Environment, Lifestyle, and Lung Function (B-WELL-Mom) study. B-WELL-Mom examines changes in asthma symptoms and control of asthma over the course of pregnancy and during the postpartum period. The study also compares lung function and immune markers for asthmatic and non-asthmatic women in relation to air pollution, dietary antioxidants, and allergies. Our research 1) assesses whether atopy (predisposition to allergic hypersensitivity) status—measured by total immunoglobulin E at the time a person enrolls in the study—predicts variability in asthma control during pregnancy; 2) evaluates whether atopy status is associated with additional decrements in lung function and increased inflammation in pregnancy among women with asthma; 3) evaluates the impact of regulatory T-cell concentrations on asthma control variability during pregnancy; and 4) evaluates changes in lung function and inflammation in all women exposed to poor ambient air quality (traffic, commuting, and ambient measures) and potential mediation by dietary antioxidants.

GWENYTH REID WALLEN, R.N., PH.D., CC

Senior Investigator and Clinical Nurse Scientist; Chief Nurse Officer; and Chief of Nursing Research and Translational Science, NIH Clinical Center

Education: University of Maryland, Baltimore (B.S.N. in nursing); Central Michigan University, Mt. Pleasant, Michigan (M.A. in management and supervision/business management); University of Maryland, College Park, Maryland (Ph.D. in public health/health education)

Training: Postdoctoral research associate, Department of Family Studies, University of Maryland (College Park, Maryland); Bravewell Fellow in Integrative Medicine, University of Arizona (Tucson, Arizona)

Before coming to NIH: Clinical nurse specialist, Neonatology, Washington Hospital Center (Washington, D.C.)

Came to NIH: In 2001 as section chief, Office of Research and Outcomes Management, Nursing and Patient Care Services, NIH Clinical Center; chief of the Research and Practice Development Service, NIH CC (2005–2009); and chief, Nursing Research and Translational Science, NIH CC (2010 to present)

Selected professional activities: Adjunct associate professor, Behavioral and Community Health, University of Maryland, School of Public Health (College Park, Maryland); adjunct assistant professor, Graduate School of Nursing, Uniformed Services University of the Health Sciences (Bethesda, Maryland); reviewer for several journals; vice chair and member of the National Institute of Child Health and Human Development’s institutional review board since 2001; collaborating with nursing colleagues in England and China to define the role of the nurse in clinical research as well as the role of the clinical nurse–scientist

Outside interests: Travelling; gardening; swimming; kayaking; boating; snorkeling

Website: https://clinicalcenter.nih.gov/about/SeniorStaff/gwenyth_wallen.html

Research interests: My clinical research focuses on health behaviors and health disparities—inequities in access to health-care services among minorities. My team and I are especially interested in the methodology and measurement in end-of-life care, integrative health, and vulnerable populations. We are testing the feasibility of health-behavior-change interventions that improve sleep quality, physical activity, and nutrition, particularly in patients with chronic diseases.

One of my earliest projects was with the NIH Clinical Center’s Pain and Palliative Care Service, studying how to provide the best possible care to cancer patients at the end of life. I am interested in working further with Ann Berger, chief of the service, who plans to open the Clinical Center’s very first Comfort Care Suite.

In a collaborative study with National Institute of Arthritis and Musculoskeletal and Skin Disease researchers, I worked with an urban community clinic that helps people with arthritis, lupus, and other rheumatic diseases. We determined that, for Hispanic patients, involving family members and spouses in the plan of care could facilitate health promotion and chronic disease management. (Clin Med Insights Arthritis Musculoskelet Disord 7:21–26, 2014; DOI:10.4137/CMAMD.S13849)

I have a strong collaboration with Tiffany Powell-Wiley at the National Heart, Lung, and Blood Institute. We are examining cardiovascular risk assessment in people from under-resourced communities. My expertise in qualitative and mixed-methods study designs provides a unique opportunity to understand the experience of at-risk individuals in their communities.

In a recently completed project, my team explored the effect of severe alcohol-use disorder (AUD) on sleep. AUDs are often accompanied by comorbid physiologic and psychosocial conditions such as anxiety, depression, post-traumatic stress disorder (PTSD), and sleep disturbances, which are associated with an increased risk of relapse to drinking after detoxification and rehabilitation.

In following up with patients who had undergone inpatient alcohol rehabilitation, we used a statistical method called latent class analysis (LCA) to see whether any group was at a higher risk of sleep disturbances. For example, we found that women with highest alcohol-withdrawal symptoms and sleep disturbances also had PTSD and higher levels of anxiety and depression. Our study showed that LCA may provide clinicians with insight into the integrative tailoring of interventions that meet the varied needs of individuals with AUDs, accompanying comorbidities, and sleep disturbances. (Behav Sleep Med, DOI:10.1080/15402002.2018.1425867; 2018).

I am also mentoring a postdoctoral fellow who is designing a collaborative study with the culinary medicine program of Tulane University (New Orleans) in which individuals are taught cooking skills and dietary practices based on the Mediterranean Diet. Evidence suggests that health behaviors improve when people participate in joint activities, such as cooking.

In addition to doing my own research, I am helping to provide more formalized fellowship opportunities for scientists from diverse backgrounds to enter and stay in the field of health-disparities research.