Cancer Biology, Pharmacology and Molecular Therapeutics Laboratories

Christensen Lab

The Christensen laboratory is focused on combining advances in molecular biology, genomics and bioinformatics with the powerful techniques of modern epidemiology and statistics to characterize epigenetic states in human health and disease. His interests include understanding relationships between epigenetic states and exposures in the context of disease susceptibility, occurrence, and progression. By investigating complex interactions between the environment and somatic epigenetic alterations in target tissues, as well as epigenetic susceptibility traits in surrogate tissues, he hopes to develop their potential translational utility for diagnostic, prognostic, and/or treatment purposes.

Cole Lab

Dr. Cole's laboratory was among the first to describe the chromosomal translocation between c-myc and the immunoglobulin locus in 1982 and has studied various aspects of Myc function ever since. The oncogenic activity of these transcription factors depends on protein domains associated with transcriptional activation, which provides an avenue to study both cancer biology and the mechanisms of gene regulation. A major contribution of the lab was the discovery of the link between Myc and E2F and the TRRAP-containing histone acetyltransferase complexes, which is currently the dominant model for the mechanism of Myc transactivation. Studies of Myc cofactors continue, but researchers also discovered another fundamental mechanism involving an unexpected aspect of gene regulation, mRNA cap methylation. A second general area of interest is the characterization of distal regulatory elements for c-myc and other critical genes involved in growth control, some of which are linked to inherited cancer risk.

Fiering Lab

Dr. Fiering's laboratory is primarily focused on in situ vaccination to generate therapeutic anti-tumor immunity

The immune system recognizes cancers and many are eliminated before they are clinically recognized. Cancer can be considered to be a failure of the immune system and it is now becoming clear that this immune failure is often due to active immunosuppression generated by the tumor.  One approach to cancer therapy is finding ways to stimulate the immune system to seek out and destroy tumor cells much like it seeks out and destroys infectious organisms.  Our lab is currently focused on developing novel approaches to boosting anti-tumor immunity by injection of immune stimulatory reagents directly into recognized tumors, an approach termed “in situ vaccination”.  The goal is to overcome the local immunosuppression, get an effective local antitumor immune response and generate a systemic antitumor immune response to fight metastatic disease. All vaccines include an antigen to be recognized by the immune system and an adjuvant to stimulate the response against the antigen.  For in situ vaccination the tumor carries all relevant antigens and injection of adjuvant into the tumor supports recognition of both tumor-associated and neoantigens expressed by the tumor. There are many options to how in situ vaccination can be performed and we explore the options in mice as well as working with dogs with spontaneous tumors and studying the local and systemic immune response involved.  The goal is to develop clinically useful in situ vaccination approaches.

Gaur Lab

Dr. Gaur's laboratory research can be broadly divided into the following three areas:

Basic Research: Understanding the critical contribution of microRNAs and their targets to various pathologies of the nervous system.

Translational Research: Running clinical trials to establish the role of microRNAs as diagnostic and prognostic biomarkers and therapeutic agents in gliomas as well as biomarkers of treatment efficacy and toxicity in glioma patients.

Biomedical Engineering: Developing innovative, in vivo wireless, nano scale devices for early detection of disease as well as regulated and targeted drug delivery.

Gerber Lab

Research in the Gerber Lab uses a combination of cell biology, biochemistry and mass spectrometry-based proteomics approaches to understand cell signaling in the cell cycle, in particular in cell division. Some of the essential effectors of cell division are oncogenes when overexpressed or dysregulated in cancer; we seek to better understand how cancer cells co-opt essential signaling pathways for survival, in the hopes of developing new therapeutic strategies

Gilbert-Diamond Lab

Dr. Gilbert-Diamond's research lab focuses on gene-environment interactions related to child health. I am currently conducting an NIH-funded study that explores the relationships between specific obesity related genotypes, brain responses (measured via fMRI) and eating behaviors.

My research lab additionally focuses on in utero exposures related to child health. With the New Hampshire Birth Cohort Study, I am studying how common exposures to arsenic and Vitamin D impact child growth and health in early life.

Havrda Lab

Dr. Havrda's laboratory studies molecular events contributing to the initiation and progression of Parkinson's disease. Investigating the neuroinflammatory activities of disease associated environmental toxins using molecular, cellular and organismal approaches.

Kettenbach Lab

Dr. Kettenbach's laboratory focuses on uncovering novel roles of phosphatases in cellular signaling networks in normal tissues and in cancer. The lab uses a mass spectrometry-based approach to study phosphatase signaling on a system-wide level in cells, and reconstitute individual components in vitro to confirm, specify and validate them.

Kinlaw Lab

Dr. Kinlaw's laboratory seeks to understand the peculiar metabolic needs of tumors, and how they adjust to them, with an eye toward exploiting tumor metabolism in the clinic. Recently focus has been on the “addiction” of tumors, including breast cancers, to a supply of fatty acids. This has led to insights related to the regulation of lipid synthesis in tumors, and the ability to target it in preclinical systems and clinical trials. The laboratory has developed unique reagents to study these pathways, including novel antibodies and genetically engineered mice. Research has also consistently focused on studies aimed to establish the relevance of findings to actual human tumors, including breast and prostate cancers, sarcomas, and lymphomas, and are involved in clinical trials of the use of unusual fatty acids to manipulate these pathways inpatients.

Kuppusamy Lab

Dr. Kuppusamy's laboratory focuses on the determination of molecular mechanisms of the role of oxygen in the disease and treatment of myocardial injury (MI), and cancer. Specifically, the lab is interested in studying oxygen-sensing mechanism and signal transduction pathways at the molecular level leading to transcriptional and post-translational regulation of p53, PTEN, and PI3K. A significant part of the research utilizes an EPR-based measurement of oxygen (oximetry).

Lau Lab

The Lau Laboratory investigates pathways that can be modulated to prevent malignant transformation or treat cancers that arise in patients with cancer predisposition syndromes. One focus of the lab is to study premalignant and malignant tissue from patients with DNA damage repair defects  (e.g. Fanconi Anemia) and determine whether the mutations in these patients result in new protein coding sequences, called neoantigens, which can be recognized as "foreign" by the patient's immune system.  Certain neoantigen profiles can predict response to therapies that work by unleashing the patient's own immune system to attack their tumor (immunotherapies).  We are using gene editing as well as mouse models to study these cancer predisposition syndromes and how their tumors respond to immunotherapies.

Leach Lab

Dr. Leach's laboratory has a long track record of research productivity in the field of pancreatic cancer biology and is known for establishing important links between pancreatic development and pancreatic cancer using both mouse and zebrafish model systems.  These include the initial discovery of abnormal Notch pathway activation as an important driver of pancreatic tumorigenesis, the identification of adult acinar cells effective “cells of origin” for pancreatic “ductal” neoplasia, the identification of a new hematopoietic-to-epithelial signaling axis required for PanIN initiation, and a detailed mapping of a unique immune neoepitope landscape associated with long term survival. Together with additional studies of pancreatic development and pancreatic epithelial plasticity, these findings have widened our view of early events in human pancreatic cancer.

Mierke Lab

Research in the Mierke laboratory aims to establish the structural basis of the mechanism of action of different peptide hormones. Particular emphasis has been placed on delineation of the interaction of the hormones with their G-protein coupled receptors employing a combination of spectroscopic techniques (NMR, EPR, fluorescence, CD), photoaffinity labeling, and extensive computer simulations. The structures provided from these efforts have facilitated the rational design of molecules with enhanced potency, receptor specificity, and duration of action.

Our laboratory is also targeting molecular scaffolds, multidomain proteins that regulate transmembrane receptor trafficking and lifetime as possible targets for cystic fibrosis, osteoporosis, and drug addiction. High-resolution NMR methods provide structural features of the protein domains, both while free and bound to the target receptor. Using novel computational approaches, this information is used to design and optimize small molecule inhibitors of the protein/receptor association.
 

Miller Lab

Dr. Miller's laboratory focuses on the translational application of knowledge of cell signaling pathways to therapeutics for breast cancer. Our work spans the spectrum of basic cancer biology, through translational studies in mouse models and human tissues, and interfaces with clinical trials. We use an array of methods and technologies both in our lab and through interaction with core facilities, including mammalian tissue culture, molecular analyses of gene and protein expression, gene expression microarrays, chromatin immunoprecipitation, next-generation DNA sequencing, bioinformatics, protein microarrays, mass spectrometry, mouse models, and live animal imaging.

Passarelli Lab

Dr. Passarelli's laboratory studies the metabolism of steroids including sex hormones, cholesterol, and bile acids in relation to the development and recurrence of colorectal polyps and cancers.

Pellegrini Lab

Research in the Pellegrini lab focuses on the characterization of protein/protein interactions based on their three-dimensional structure, with the goal to modulate, interfere with or inhibit the protein biological function. Structural efforts in the lab employ both Nuclear Magnetic Resonance and X-ray crystallography, complemented by tools from molecular biology, biochemistry and a number of biophysical techniques for the characterization of molecular interactions, including Circular Dichroism and Fluorescence Anisotropy. A major track of our research addresses the role of the scaffolding protein NEMO in the NF-κB pathway and the characterization of its molecular interactions, with a view to develop peptidic and small molecule antagonists to modulate its function. NEMO inhibition was shown to be a promising therapeutic avenue in diseases correlated with NF-κB hyperactivation including inflammatory and autoimmune diseases and many cancers.

Pioli Lab

The Pioli lab is focused on identifying the molecular mechanisms that regulate macrophage activation in the context of both autoimmunity and cancer. Taking advantage of macrophage plasticity, we then use this information to determine how macrophage activation can be altered for maximal therapeutic benefit.

Raman Lab

Dr. Pattabiraman's research focuses on understanding the genetic, epigenetic, signaling and cell biological aspects of tumor progression and metastasis in carcinomas. We study the role of transitions in epithelial and mesenchymal states within carcinomas as a model of understanding intratumoral heterogeneity to develop novel ways of overcoming metastatic progression and therapy resistance.

Sanchez Lab

Dr. Sanchez's laboratory studies checkpoint signaling events triggered during the response to DNA damage or replication interference, how they regulate cell cycle progression, DNA repair and cell death. The role of checkpoints in the etiology of cancer and as drug targets for therapeutic enhancers of genotoxic cancer drugs.

Stan Lab

The Stan laboratory studies the role of blood vessels in the pathogenesis of inflammatory disease and cancer. Using a broad variety of experimental approaches (e.g. genetically modified mouse models, cell biological approaches in cell culture and fluorescence and electron microscopy), our lab studies the biology of specific vascular endothelial gene products (i.e. PLVAP and interacting partners) and endothelial specific structures (e.g. fenestrae, caveolae, and vesiculo-vacuolar organelles) in normal cardiovascular function and the adaptive responses that occur in disease. A significant part of our work is devoted to developing novel therapeutic and diagnostic strategies for inflammation and cancer.

Tsongalis Lab

Dr. Tsongalis is the Director of the Laboratory for Clinical Genomics and Advanced Technologies (CGAT) at the Geisel School of Medicine. His area of expertise is in clinical molecular diagnostic applications. His research interests are in the pathogenesis of solid tumors, disease association of SNP genotyping and personalized medicine. 

Wang Lab

Current research in the Wang lab is focused on studying the genome-wide targeting of SWI/SNF complex in cancer and its role in regulating chromatin structures; identifying novel interacting proteins and co-regulators; searching for cancer specific vulnerabilities using genome-wide CRISPR-Cas9 screens.