The Laboratory of Cancer Biology and Genetics (LCBG) self-assembled in 2006 through the merger of the Laboratory of Cellular Carcinogenesis and Tumor Promotion (LCCTP), the Laboratory of Cell Regulation and Carcinogenesis (LCRC) and the Laboratory of Genetics (LG). The LCBG currently encompasses the work of 12 principal investigators supervising independent research programs with highly overlapping experimental goals and approaches. These investigators conduct a well integrated research program consisting of basic and translational components that are designed to: elucidate the cellular and tissue changes associated with specific stages of carcinogenesis, detect and characterize genetic modifiers fundamental to cancer susceptibility and progression, define the molecular mechanisms involved in the pathogenesis of major human cancers, and develop rational approaches for cancer prevention and treatment. Studies are performed in vivo in animal models, in vitro in cell and organ culture, and on tissues and cells obtained from human volunteers and cancer patients. The LCBG also develops and correlates novel protocols in molecular diagnostics for human and animal tissues, and in noninvasive medical imaging for animal models. Emanating from our studies are new therapeutic combinations for targeted cancers now in clinical trials. The LCBG operates a novel University-NCI graduate partnership research training program in comparative molecular pathology, including both Ph.D. granting and non-degree fellowships.

Investigators

The research focus of the LCBG principal investigators is as follows:

Steven Cappell, Ph.D., focuses on understanding  the cellular and molecular mechanisms underlying cell cycle regulation at the single-cell level. In particular, he applies state-of-the-art live-cell imaging approaches and fluorescent biosensors to dissect the dynamic signaling pathways controlling the G1 to S phase transition. His work has shed new light on how cells make the decision to proliferate and the origin of cell-to-cell heterogeneity.

Jing Huang, Ph.D., has focused his research program on the epigenetic mechanisms underlying cancer and stem cells, has used genomics to uncover a role for the tumor suppressor p53 in regulating the differentiation of embryonic stem cells during DNA damage.

Kent Hunter, Ph.D., is a pioneer in systems genetics, having demonstrated first in mouse models, and confirming by association studies in cancer patients, that an individual's genetic background has a significant effect on the propensity of their tumors to metastasize; his work has established a new paradigm of inherited susceptibility in metastasis research.

Kenneth Kraemer, M.D., investigates the role of DNA repair in prevention of cancer and in human development. The approach involves integrated clinical, molecular, and translational investigations of disorders with defective DNA repair. Current studies are focusing on two rare genetic diseases: xeroderma pigmentosum (XP) a cancer-prone genetic disease with cellular hypersensitivity to ultraviolet radiation (UV) and defective DNA repair and trichothiodystrophy (TTD) a disorder with developmental abnormalities and defects in some of the same genes as XP without increased cancer risk.The long-term goals are to: 1) define the molecular defects in these diseases, 2) characterize their clinical abnormalities and extent of phenotypic heterogeneity, 3) correlate the molecular defects with clinical abnormalities, 4) assess the altered molecular function, 5) identify and characterize the underlying mechanisms (pathophysiology) and how they lead to clinical disease, and 6) influence these processes by exploring methods of cancer prevention.

Ji Luo, Ph.D., focuses on understanding the biology of cancers with mutations in the KRAS oncogene. In particular, he applies functional genomics approaches to dissect genetic dependencies and delineate mechanisms of non-oncogene addictions in KRAS mutant cells in order to identify new therapeutic modalities.

Glenn Merlino, Ph.D., has made key contributions to several areas of basic research, including receptor tyrosine kinase signaling, oncogenic transformation, transcription regulation, cell cycle regulation, and genomic instability, and is now developing new preclinical tools and approaches to determine how metastatic cells survive therapy and recur at distant sites.

Beverly Mock, Ph.D., investigates genetic susceptibility to mouse plasma cell tumors as a model system for analyzing complex genetic traits associated with cancer, and has identified four separate loci on two chromosomes that are involved in tumor susceptibility, including genes encoding Mndal, p16INK4a and mTOR. Drug combinations targeting the mTOR and p16 pathways are showing synergy in intervention studies. 

Meera Murgai, Ph.D., focuses on understanding the role of perivascular cells and other stromal cells in promoting metastasis. Most recently, her efforts have focused on employing single cell sequencing, immunofluorescent imaging, computational methods, and lineage tracing to elucidate the stromal cell populations that play pro- and anti-tumor roles in pre-metastatic and metastatic microenvironments. Her work has uncovered a previously underappreciated role for perivascular cells to initiate pre-metastatic niche formation.

Mark Simpson, D.V.M., Ph.D., with specialty board certification by the American College of Veterinary Pathologists, has established and directs a unique University-NCI graduate partnership research training program in comparative molecular pathology. The Comparative Biomedical Scientist Training Program provides interdisciplinary training for veterinarians in both diagnostic pathology and human disease-oriented medical research in order to increase the synergy for comparative biomedical research interactions and animal model predictability.

Lalage Wakefield, D.Phil., uses mouse models and genomic approaches to address the critical, complex dual role played by transforming growth factor-beta (TGF-beta) in breast cancer progression, in regulating breast cancer stem cell dynamics, and to develop TGF-beta-based therapeutic strategies.

Li Yang, Ph.D., has focused her research on dissecting the cellular and molecular mechanisms underlying the metastatic process, with a focus on inflammation and tumor microenvironment. She has demonstrated that the recruitment of immature myeloid cells to the tumor microenvironment is responsible for the switch of TGF-beta signaling from tumor suppressor to tumor promoter.

Emeritus Investigators

Stuart Yuspa, M.D., has a longstanding interest in mechanisms of carcinogenesis with particular emphasis on signaling pathway alterations in premalignant lesions. His laboratory utilized mouse skin carcinogenesis models to study molecular events that determine the phenotypic evolution of normal keratinocytes through a benign tumor stage and conversion to squamous cell carcinoma.

Miriam Poirier, Ph.D., is a pioneer in biochemical dosimetry and molecular epidemiology, having introduced to the field highly sensitive immunoassays to detect DNA damage caused by carcinogenic chemicals, and investigates the extent and consequences of DNA damage caused by exposure to environmental agents and  pharmaceuticals, using experimental models and human subjects to elucidate mechanisms of cancer causation and prevention.                                           

Adjunct Investigators

Zheng-Gang Liu, Ph.D., from the Laboratory of Immune Cell Biology, is a renowned researcher in the fields of tumor necrosis factor (TNF) signaling and the regulation of apoptosis and necrosis. He has made several seminal findings to the current understanding of TNF signaling and the mechanisms of cell death.

Mary Ann Stepp, Ph.D., is Professor of Anatomy and Cell Biology and Professor of Ophthalmology at the George Washington School of Medicine and Health Sciences and an Adjunct Investigator in LCBG. Studies in her laboratory focus on the epithelial wound repair in the cornea and skin and in the restoration of tissue function after injury.  In vivo mouse models for recurrent epithelial erosions and corneal epithelial stem cell deficiency have been developed and used to study integrin, laminin, and proteoglycan expression in vivo and in vitro after injury to develop treatments for erosions. Currently, her lab has begun to focus on sensory nerve regeneration in the cornea to develop insights into the causes of small fiber neuropathy. For more information, visit the Stepp Lab.

Wendy C. Weinberg, Ph.D., is Senior Investigator and Chief of the Laboratory of Molecular Oncology in the Office of Biotechnology Products, CDER/FDA. She has been an Adjunct Investigator in LCBG since 2016. Studies in the Weinberg laboratory are focused on the contribution of TP63 gene dysregulation that is associated with squamous cancer pathogenesis and elucidating downstream and interacting pathways, in particular NFkB/c-Rel and RAS. Her laboratory has also established in vivo models to evaluate the immune microenvironment during squamous cancer progression to delineate molecular attributes of targeted antibodies and immune checkpoint inhibitors that are critical to clinical efficacy of these biotechnology derived therapies. 

Maria I. Morasso, Ph.D., is the Chief of the Laboratory of Skin Biology in NIAMS and an Adjunct Investigator in LCBG. Studies in her laboratory have combined molecular, cellular and bioinformatic approaches and determined essential roles for theDLX3, SOX2 and PITX1 factors in coordinating the transcriptional networks that regulate skin differentiation and wound healing. Her group is focused on how deregulation of these networks leads to skin disorders, such as squamous tumor growth, skin inflammatory diseases and non-healing wounds. The complementary use of human and mouse models allows for validation of the potential efficacy in translating the research findings to human conditions through the development of potential therapeutics.