Colleagues: Recently Tenured

DONALD COOK, PH.D., NIEHS

Senior Investigator, Immunogenetics Group, Laboratory of Respiratory Biology

Education: McGill University, Montreal (B.S. and Ph.D. in microbiology and immunology)
Training: Department of Pathology, University of North Carolina at Chapel Hill School of Medicine (Chapel Hill, N.C.)
Before coming to NIH: Principal scientist, Schering-Plough Research Institute (Kenilworth, N.J.); assistant professor, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center (Durham, N.C.)
Came to NIH: In 2005 as a tenure-track investigator
Selected professional activities: Editorial board for American Journal of Respiratory Cell and Molecular Biology and Frontiers in Chemoattractants; adjunct assistant professor, Department of Immunology, Duke University School of Medicine
Outside Interests: Training for short triathlons; playing blues on the piano

Research Interests: My lab uses gene-targeted mice lacking chemokines, cytokines, or signaling molecules to understand the molecular and cellular mechanisms that trigger immune responses to inhaled allergens. Much of our work focuses on pulmonary dendritic cells, which are highly specialized cells that present inhaled antigens to T lymphocytes, thereby initiating immune responses to aeroallergens. Dendritic cells in the lung are heterogeneous; they develop from different precursor cells and have epigenetic modifications that restrict their function. By purifying discrete populations of dendritic cells from the lung, we have been able to assign specific functions to each population.
We also study how these functions are affected by gene-environment interactions. For example, we have found that bacterial products, such as lipopolysaccharide and flagellin, can be found in common house dust and promote distinct types of allergen-specific immune responses. We also examine how environmental agents affect the function of epithelial cells that line the airway.

We are currently testing the hypothesis that communication between airway epithelial cells and nearby dendritic cells ultimately determines the nature of immune responses to inhaled allergens. An improved understanding of these signaling pathways offers the potential for developing therapeutic strategies that target specific types of asthma, including steroid-resistant asthma.

STEVEN S. VOGEL, PH.D., NIAAA

Senior Investigator; Chief, Section On Cellular Biophotonics, Laboratory of Molecular Physiology

Education: City College of New York, New York (B.S. in biology); Columbia University, New York (Ph.D. in biochemistry and molecular biophysics)
Training: Postdoctoral training at NIDDK, NICHD, and NINDS
Before returning to NIH: Associate professor and director of the Cell Imaging Core Laboratory at the Medical College of Georgia (Augusta, Ga.)
Came to NIH: In 1989 for training; in 2003 joined NIAAA
Selected professional activities: University of Virginia FRET Microscopy Workshop Faculty (2006–present)
Outside interests: Playing acoustic 6– and 12–string guitar; bicycle commuting

Research interests: In cells, proteins rarely function in isolation; they act together to form assemblies that mediate cellular processes. Considering that protein complexes are so ubiquitous and that they perform so many functions, it is no surprise that many human diseases arise from inappropriate protein interactions. A major obstacle to understanding the basis of these diseases, however, is the paucity of robust methods for studying both normal and abnormal protein interactions under physiological (natural) conditions.

Through my research, which lies at the intersection of physics, bioengineering, and neurobiology, I have been trying to develop new forms of fiber-optic microscopy and spectroscopy to better monitor protein interactions inside living cells and animals. These approaches are based primarily on Förster resonance energy transfer (FRET) and fluctuation correlation spectroscopy (FCS). I am especially interested in the interactions of synaptic proteins that are involved in regulating memory, behavior, and addiction.
My long-term goal is to use FRET and FCS to help identify drugs that can target and correct abnormal protein interactions inside cells. The technology that we are developing will provide tools for delineating the steps in protein-complex conformational changes; a means of rapidly identifying sites of protein interactions; a way to help decipher which protein partners interact within large assemblies of proteins; and the means for confirming whether specific interactions occur under physiological conditions even when those interactions occur deep within the brain of a living mouse.

KYLIE WALTERS, PH.D., NCI-CCR

Senior Investigator; Head, Protein Processing Section, Structural Biophysics Laboratory

Education: Wesleyan University, Middletown, Conn. (B.A. in molecular biology and biochemistry and concentration in biophysics); Harvard University, Cambridge, Mass. (Ph.D. in biophysics)
Training: Postdoctoral training in pathology at Harvard Medical School (Boston)
Before coming to NIH: Associate professor of biochemistry, molecular biology, and biophysics, University of Minnesota (Minneapolis)
Came to NIH: In July 2013
Selected professional activities: Has served as NIH Membrane Biology and Protein Processing study section member since 2008
Outside interests: Enjoys outdoor activities with husband and two children; swimming; kayaking and canoeing; running

Research interests: We use nuclear magnetic resonance (NMR) and other biophysical techniques to reveal the three-dimensional structure and dynamic properties of proteins and complexes associated with cancer biology. We are particularly interested in ubiquitin signaling pathways, especially those involved in protein quality control. Ubiquitins, small regulatory proteins that become attached to other proteins through an enzymatic cascade, regulate gene transcription, protein degradation, cell death, and other cellular activities. We study how misfolded proteins are recognized and cleared from cells and how targeted ubiquitinated proteins are identified and processed by the proteasome.

The proteasome is the major machinery in eukaryotes (organisms whose cells contain a nucleus and other organelles) for regulating protein degradation. It contains enzymes called proteases, which degrade protein substrates. The proteasome can be “capped” by multiple regulators. We focus on the 19S regulatory particle, which contains the proteins that recognize and process ubiquitinated substrates. Human pathologies associated with malfunctions of the ubiquitin-proteasome pathway include autoimmunity and inflammation, neurodegeneration, and cancer. The proteasome inhibitors bortezomib and carfilzomib are used to treat certain hematological cancers; other inhibitors are being tested in clinical trials. Our long-term goal is to reveal quality-control mechanisms in the ubiquitin-proteasome pathway in order to manipulate the lifespan of oncoproteins and tumor suppressors.

KATHERINE WARREN, M.D., NCI-CCR

Senior Investigator; Head, Pediatric Neuro-Oncology Section, Pediatric Oncology Branch

Education: North Adams State College, North Adams, Mass. (B.S. in medical technology); Tufts University School of Medicine, Boston, Mass. (M.D.)
Training: Residency in pediatrics at Children’s National Medical Center (Washington, D.C.); fellowship in pediatric hematology and oncology at NCI
Came to NIH: In 1993 for training; became a tenure-track investigator in 2003
Selected professional activities: Active in the Pediatric Brain Tumor Consortium (holds leadership positions) and the Children’s Oncology Group
Outside interests: Spending time with family; traveling

Research interests: I am interested in developing better treatments for children who have tumors of the central nervous system (CNS). Pediatric CNS tumors differ from adult CNS tumors in histology, biology, pathophysiology, and location, so data from adults may not apply to pediatric patients. We are conducting clinical trials to test the biologic and therapeutic activity of new agents for treating CNS tumors in children; exploring new methods of treatment delivery to the tumor site; noninvasively evaluating and imaging the brain to assess tumor characteristics; and studying neurotoxicity resulting from tumor treatment.

A significant proportion of pediatric brain tumors are benign or low-grade, and the five-year survival rate is over 70 percent. But the survival rate is dismal for children with malignant tumors such as diffuse intrinsic brainstem gliomas, high-grade gliomas, and recurrent malignant tumors.Treatments for pediatric CNS tumors include surgery, radiation, and chemotherapy. Chemotherapy is not always successful, however, because the blood-brain barrier limits the delivery of the drugs to the tumor site. And such treatment has little, if any, effect on malignant gliomas and recurrent malignant tumors, and it has no effect against the brainstem tumor diffuse intrinsic pontine glioma (DIPG). Surgery is not an option for DPIG because of the tumor’s location in the brainstem, which controls vital functions such as heartbeat and breathing. Most children with DIPG die within one year of diagnosis.

Although hundreds of clinical trials have been performed with DPIG over three decades, there’s been no progress in improving outcomes in these children. We know little about the biology of this disease partly because biopsies are not routinely obtained in the United States so there’s a scarcity of tissue available for study. My research on these tumors has focused on developing new agents for treatment; doing noninvasive evaluations; using autopsy tissue to study tumor biology; and developing novel approaches to deliver chemotherapeutics directly.

NICOLAS WENTZENSEN, M.D., PH.D., M.S., NCI-DCEG

Senior Investigator, Hormonal and Reproductive Epidemiology Branch

Education: Heidelberg University Ruperto Carola, Heidelberg, Germany (M.D. and Ph.D. in applied tumor biology); Johannes Gutenberg University of Mainz, Mainz, Germany (M.S. in epidemiology)
Training: Residency in general surgery and postdoctoral research in applied tumor biology and molecular epidemiology, Heidelberg University; postdoctoral research in NCI-DCEG
Came to NIH: In 2007 as a visiting fellow; became tenure-track investigator in 2009
Selected professional activities: Senior editor, Cancer Epidemiology, Biomarkers and Prevention; member of the Practice Improvement in Cervical Screening and Management Working Group that developed new cervical cancer screening guidelines and co-author of the 2012 consensus cervical cancer screening-guidelines publications; member of the steering committee, working-group leader, and writing team member for the 2012 American Society for Colposcopy and Cervical Pathology management-guidelines update; faculty of various international scientific conferences
Outside interests: Running; listening to classical music; playing guitar

Research interests: I am interested in the origins of gynecologic cancers and improving screening and prevention efforts. My research focuses on understanding the heterogeneous etiology of cervical, endometrial, and ovarian cancers and their precursors. I am analyzing risk factors that drive the development of these malignancies and looking at biomarkers that could identify women at high risk.

Although most cervical cancers are caused by human papillomavirus (HPV) infections, only a small subset of women infected with HPV progress to invasive cancer. We are conducting profiling studies on more than 2,000 tissue samples collected from women with cervical HPV infections, precancer, and cancer to elucidate the transitions from cervical HPV infection to precancer and from precancer to invasive cancer.

We are also interested in improving colposcopy-guided biopsy procedures, which are used to screen for cervical cancer but tend to be inaccurate and frequently miss the worst lesions on the cervix. We conducted the Biopsy Study, to quantify the inaccuracy of colposcopies. We also hope to expand our understanding of the clonal relationship of multiple lesions on the cervix.

In addition, we are exploring the etiology of ovarian cancer, which is complex, poorly understood, and often fatal. Because the low prevalence of ovarian cancer limits molecular epidemiology studies, we are pooling cases from several NIH-based and extramural cohorts. We are conducting large epidemiologic studies and profiling ovarian tumor tissues. We hope to improve the classification of ovarian tumors and evaluate new early-detection approaches that can be translated into clinical or screening applications. In other studies, we are investigating how inflammatory markers and endogenous hormone exposures to ovarian epithelium promote tumor growth.