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Molecular Medicine - Open Positions

Translational and Clinical Research

Program in Molecular Medicine Faculty are dedicated to not just developing a deeper understanding of biology and biological processes but also taking this deeper understanding into the clinic in order to 1) develop new therapies and vaccines for non-infectious and infectious diseases around the world and 2) elucidate the etiology and epidemiology of human diseases through clinical research. Our goal is to use biology and biological research to better human life.  Examples include developing new therapies for autoimmunity (e.g., Type 1 diabetes, Scleroderma, IBS), cancer, infectious diseases (e.g, SARS-CoV-2, HIV, Epstein- Barr Virus, tuberculosis, helminths), metabolic disorders (e.g., Type 2 diabetes, hepatic steatosis, lipodystrophy, tyrosinemia), and neurodevelopmental and degenerative diseases (e.g., Fragile X, Huntington’s, epilepsy, microcephaly, obsessive compulsive disorder, and muscular atrophy).

Epigenetics, chromosome dynamics, and diseaseral

Eukaryotic genomes are condensed into chromatin fibers in order to fit over a meter of DNA within the limited volume of the nucleus.  However, chromatin assembly limits the accessibility of genomic sequences and creates inherent barriers for nuclear events such as transcription, DNA replication, and DNA repair.  Consequently, chromatin structure must be dynamic or fluid, and local changes in chromatin structure are regulated to provide the cell with profoundly effective methods for fine-tuning DNA metabolism. Different chromatin states can be inherited by progeny after cell division, providing epigenetic regulation of both coding and noncoding RNAs that control cell function and identity. Not too surprisingly, disruption of mechanisms that control chromatin dynamics can lead to aberrant gene expression, improper or nonexistent DNA repair, chromosomal translocations, inappropriate proliferation, developmental errors, oncogenesis, or even cell death. Scientists in the Program in Molecular Medicine are investigating these mechanisms in detail, uncovering new insights that are enabling the development of therapeutic strategies for attacking cancer and other major diseases.

Developmental, Regenerative and Stem Cell Biology

Within our genome is encoded all of the information needed to create a person.  Complex genetic, molecular and cellular mechanisms use this information to drive the proliferation, differentiation and migration of cells to form tissues, organs and organisms.  Understanding these processes is paramount in our understanding of disease pathogenesis and the development of regenerative therapies for diabetes, kidney disease, blindness, neural degeneration and aging.  Program in Molecular Medicine research programs cover a broad range of developmental events employing model organisms ranging from unicellular organisms to invertebrates, flies, worms, rodents and humans.

Obesity and Diabetes

Adipose tissue in human subjects has the remarkable and unique property of being able to expand to 100 pounds or more during the development of obesity. This expansion involves hundreds of fascinating pathways that are coordinated to store fat within adipocytes. These include activation of genomic networks through chromatin remodeling, epigenetic regulation of gene expression, cell proliferation and differentiation, cell signaling and trafficking, infiltration of immune cells into adipose tissue and crosstalk between adipocytes and neurons. Hidden within these various mechanisms of adipose expansion is the mystery of why some obese humans develop type 2 diabetes while others at the same weight do not. This is a mystery of enormous importance since most people in the US are overweight or obese, and the incidence of diabetes is a staggering 9% of the population. Investigators in the Program in Molecular Medicine are tackling the mechanisms in metabolic tissues that go awry in obesity and lead to the onset of diabetes. Recent advances include the discovery of how to culture unique human adipocytes that are specialized to burn fat rather than store it, as well as discoveries of signaling pathways that activate these fat burning cells. These and other findings have provided strategies for the prevention and treatment of obesity and type 2 diabetes.

Host Pathogen Interactions: Microbiology, Infection, and Immunity

Development of a wide array of biochemical, genetic, molecular biology, and epidemiologic, and “omic” techniques enable experiments that teach us about the pathogens themselves, about ourselves, and about such fundamental biological mechanisms as transcriptional regulation and evolution. Investigators working within the Program in Molecular Medicine study a wide-range of pathogens, including Dengue Virus, Ebola virus, Epstein-Barr Virus, HIV-1, SARS-CoV-2, Zika virus, Vibrio cholera, Mycobacterium tuberculosis, as well as nematode parasites that include hookworms, whipworms and Ascaris. Exciting initiatives are moving discoveries of basic mechanisms into strategies for therapies.

RNA Biology

In addition to protein-coding mRNAs, genomes produce a wide variety of non-coding RNAs, which function in a vast array of cellular processes, including all aspects of gene expression and its regulation. The study of RNA Biology focuses on understanding the mechanisms of RNA interference, a form of sequence-specific gene silencing triggered by double-stranded RNA, functions of microRNAs that control timing of organism development, RNA splicing mechanisms and noncoding RNA actions, mRNA translational control, and the role of piRNAs in maintenance of germline integrity. Recent discoveries on the role of RNA in gene editing, including mechanisms of CRISPR, are also proceeding at a rapid pace. RNA biologists in Molecular Medicine have made striking discoveries in novel types of RNA and their mechanisms of action, and are investigating the role of RNAs in a variety of human diseases such as cancers, diabetes, autism and Fragile X.

Oncogenes and Cancer Biology

Cancer is one of the leading causes of death worldwide, and it is estimated that approximately one out of every three people will be diagnosed with cancer in their lifetime. The primary goal in cancer biology is to understand more about what makes cancer different than normal, in order to identify strategies to selectively eradicate these abnormal cells. In its basic tenets, cancer is a set of related diseases caused by genetic mutations that dysregulate cell growth and survival. Although every cancer subtype is distinct, these mutations produce a set of “hallmark” traits that are shared by all cancers. For example, cancer cells have unlimited proliferation capability and tend to grow rapidly. They have gained the ability to block immune responses and to evade cell death. And they have changed the rules that regulate growth/survival/movement in normal cells, to facilitate their dissemination and colonization of distant parts of the body.

The human genome contains functional elements and protein encoding genes that are translated into proteins. Regulation of gene expression by functional elements produces specific patterns of expression in different tissues and cell types making each individual unique. It is however not currently possible to assess the impact of mutations or environmental changes that affect these genes or DNA elements that control them.  Molecular Medicine investigators use a wide array of genetic, biochemical, biophysics, X ray crystallography, cryo-EM and systems biology techniques to dissect the complex regulatory networks associated with disease states like cancer, diabetes, infectious diseases and neurodevelopmental disorders.

Precision Medicine: Computational and Structural Biology

Research by investigators in Molecular Medicine aims to discover genes that regulate tumorigenesis, to understand the basic regulation of biological processes that are altered in cancer cells and to improve our ability to identify, prevent, and treat various forms of cancer.