Biochemistry

Welcome to the Department of Biochemistry at Boston University School of Medicine. We are a highly interactive group of faculty, graduate students, and postdoctoral fellows with diverse research interests in biochemistry, cell biology, molecular biology and genetics. We use cutting-edge technologies and experimental systems to address the cellular and molecular mechanisms of biological processes, particularly those that relate broadly to human disease. Specific research themes within the department include Neuroscience & Aging; Signal Transduction & Cancer; Extracellular Matrix/Cellular Injury; Metabolism, Obesity/Diabetes; Proteomics & Glycomics; and Development (see below for more information about our research).

The Department of Biochemistry is part of a large medical school/hospital complex that includes state-of-the-art laboratories, mass spectrometry resources, confocal laser scanning microscopy and transgenic animal facilities. Under the direction of our Chair, Dr. David A. Harris, our department has embarked on an exciting expansion initiative, with the recruitment of new faculty members and substantial renovation of our research laboratories.

Our faculty are committed to the education of graduate, medical and dental students. As part of the Division of Graduate Medical Sciences, the Department of Biochemistry currently offers the following degree programs: Doctor of Philosophy (PhD) (post-bachelor’s and post-master’s PhD) and a combined Doctor of Medicine degree with a PhD (MD/PhD). This year, we launched an interdisciplinary, “umbrella” program called the Program in Biomedical Sciences (or PiBS for short).

Our graduate programs incorporate didactic coursework and biomedical research to prepare our graduates for career advancement. Our Foundations in Biomedical Sciences (FiBS I) and Professional Development & Mentoring curricula have been integrated into this new program. During the first year in the PiBS program, while taking classes, students rotate in a number of research laboratories, enabling the selection of a dissertation research laboratory. Students will join the program/department with which the mentor is affiliated and continue advanced studies towards candidacy. The didactic coursework includes our FiBS core classes that incorporate principles of biochemistry, cell biology, molecular biology and genetics. Additional course material includes laboratory techniques, statistics and advanced electives.

In addition to the biomedical science coursework mentioned above, our new Professional Development & Mentoring curriculum offers credit-bearing coursework as well as workshops to enable our graduates to pursue careers in a variety of sectors, including research and non-research careers in academia, biotechnology, government, or wherever they may choose to work after Boston University.

Students applying for acceptance into the PhD program apply directly to PiBS. More information about the program can be found on our website. Students applying for acceptance into the MD/PhD program can find more information about the program and the application process on our website.

Please return to our website frequently or contact us to learn more about our graduate programs and research discoveries.

Research

Neuroscience & Aging

The medical, social, and economic impact of age-related diseases is immense, and is increasing rapidly as life expectancy is extended and the average age of the population shifts upward. Aging is associated with increased risk of developing disorders such as atherosclerosis, heart disease, diabetes, cancer, and neurodegenerative conditions including Alzheimer’s, Parkinson’s and prion diseases, which are due to protein misfolding and aggregation in the brain. At a mechanistic level, these disorders are related to alterations in key physiological, cellular and molecular pathways, including those related to metabolism, cellular proliferation, inflammation, neuronal plasticity, protein folding and quality control, and protein trafficking and degradation. The Department of Biochemistry offers graduate students exciting opportunities to study age-related diseases in a variety of cellular and animal systems.

Faculty conducting research in these areas:

  • Carmela Abraham (Normal aging and Alzheimer’s)
  • Catherine Costello (Amyloidosis)
  • David A. Harris (Prion diseases)
  • Peter Polgar (Vascular disease and aging)
  • Brigitte Ritter (Receptor trafficking)
  • Michael Sherman (Amyloidosis in Huntington’s)

Signal Transduction & Cancer

Cancer is a class of diseases (also known as malignant neoplasms) in which normal cellular homeostasis is lost and a group of abnormal cells divide without control or stop responding to normal restraint in growth. In addition to uncontrolled growth, these cells can also display invasion (intrusion on and destruction of adjacent tissues) and sometimes metastasis. In the United States, cancer accounts for one of every four deaths. The American Cancer Society estimates more than half a million Americans die of cancer every year (>1,500 people a day). Human cancers develop through successive genetic and epigenetic changes that confer tumor cells the ability to grow uncontrollably and eventually invade other organs. Most cancers arise sporadically due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals or infectious agents and a smaller proportion (~10%) are a direct consequence of inherited genetic abnormalities.

Genes whose dysregulation trigger cancer are classically divided into two classes: oncogenes and tumor suppressor genes. Upregulation of the function of oncogenes or downregulation of tumor suppressor genes promote cancer progression by giving cells new properties such as hyperactive growth and division, protection against programmed cell death, loss of respect for normal tissue boundaries and immunological control, error prone DNA replication and the ability to invade other tissues. Oncogenes and tumor suppressor genes not only encode for proteins that form part of the structural core of these processes (e.g., DNA repair proteins, cell division machinery, etc), but also for those that control the signal transduction mechanisms by which this processes are regulated in response to external stimuli (e.g., surface receptors, kinases, etc). Further understanding of cancer cell biology is critical to develop novel and more effective strategies for diagnosis and therapy. Work in several laboratories of our department is devoted to dissect the molecular basis of different cancer-related processes and thereby contribute to the race for the cure of this disease.

Faculty conducting research in these areas:

  • Mikel Garcia-Marcos (G protein signaling)
  • Kathrin H. Kirsch (Cell signaling)
  • Matthew Layne (Cancer associated fibroblasts and the stromal reaction)
  • Zhijun Luo (Tumor growth and metabolism)
  • Valentina Perissi (Transcriptional coactivators)
  • Brigitte Ritter (Receptor trafficking)
  • Michael Sherman (Cell Senescence, cell stress)
  • Bob Varelas (Development and cancer)

ECM/Cellular Injury

Critical to the evolution of multicellular organisms was acquiring the ability to synthesize connections between cells. The extracellular matrix (ECM) integrates cells into tissues, tissues into organs, and organs into the organism. The ECM is an extension of the cell and participates actively in functions including development, migration, proliferation, metabolism and stabilization of tissue structure. Just as connective tissue was critical to the evolution of multicellular organisms, so too has evolution of multicellular organisms left them dependent upon connective tissue so that the ECM is associated with a wide range of diseases.

Cardiovascular disease is the number one cause of death in the United States. Vascular injury leads to chronic inflammation of the vasculature, causing atherosclerosis or lesion formation that leads to cardiovascular events. Likewise, injury and inflammation in the lung compromise its properties. Researchers in the Department of Biochemistry have identified basic elements of the mechanisms of vascular injury and lung fibrosis that contribute to cellular dysfunction, with emphasis on the role of the extracellular milieu.

Faculty conducting research in these areas:

  • Matthew Layne (Transcriptional regulation, atherosclerosis, lung fibrosis)
  • Peter Polgar (Receptor structure/function)
  • Barbara Schreiber (Elastin, serum amyloid A, atherosclerosis)
  • Barbara Smith (Collagen, transcriptional regulation, atherosclerosis, lung fibrosis)
  • Vickery Trinkaus-Randall (Glycosaminoglycans)
  • Joseph Zaia (Glycosaminoglycans)

Metabolism, Obesity/Diabetes

The modern world is in the midst of an obesity epidemic that is growing to the extent that, in 2003–2004, 32% of U.S. adults were obese and more than 50% were overweight, numbers that have been growing ever since. This dramatic increase in body weight has led to a significant upsurge in the number of individuals with obesity-related disorders, including Type-2 Diabetes, cardiovascular disease, hypertension, and dyslipidemia. A worrying trend is that adolescents are also becoming obese and, consequently, are succumbing to metabolic diseases that a decade ago occurred in adults only. Awareness of this trend has stirred a significant effort to understand more about the link between adiposity and metabolic disease.

Physiological control of metabolism involves an elaborately coordinated process involving cross-talk between several organs and tissues that regulate the production of hormones and the metabolism of lipids and glucose. In an effort to gain a greater understanding of the control of energy balance, investigators in the Department of Biochemistry are attempting to identify the molecular mechanisms within each tissue that contribute to the overall control of metabolism. This research has included defining the signaling pathways and transcriptional events that specify production and action of metabolically important hormones and cytokines.

Faculty conducting research in these areas:

  • Stephen R. Farmer (Transcriptional control of adipocyte formation and function)
  • Konstantin Kandror (Cell biological aspects of insulin signaling)
  • Matthew Layne (Adipose tissue formation and fibrosis)
  • Valentina Perissi (Transcriptional coactivators)
  • Paul F. Pilch (Vesicular traffic related to insulin action, caveolae, lipodystrophies)
  • Barbara Schreiber (Inflammation and smooth muscle cell lipid metabolism)

Proteomics & Glycomics

Proteomics projects comprise the use of mass spectrometric methods for determining patterns of protein expression in biological systems. Effort is underway to develop proteomics methods and apply these to collaborations at BUMC and around the world. Example projects include:

  • Targeted proteomics for detecting cardiovascular disease and metabolic causes
  • Imaging mass spectrometry of brain tissue in neurological diseases

Glycoproteomics involves the study of structural and functional aspects of protein glycosylation. Many mammalian proteins contain glycan binding domains that interact with specific classes (known as epitopes) of glycoprotein glycans. The functions of glycoproteins, by virtue of the proteins to which they bind, depend heavily on context-depended glycans with which they are modified. Effort is underway to develop and apply effective methods for glycoprotein analysis to meet the needs of biomedicine. Projects include:

  • Top-down mass spectrometry of glycoproteins and clinically relevant proteins
  • The roles of glycosylation in influenza A virus infectivity

Glycomics is the study of the structures and functions of glycans in biological systems. Glycans function in biomedicine according to the proteins (or protein domains) to which they bind. All cells are coated with a dense layer of glycans, through which all molecular interactions take place. Effort is underway to develop and apply methods for analyzing glycans related to human disease questions. Projects include:

  • Glycomics of glycosaminoglycans
  • Elucidation of the glycan structures of methanogenic archaea
  • Identification of glycans in human milk that are protective against HIV infection
  • Activated electron dissociation tandem mass spectrometry of glycans
  • Development of software for interpretation of glycan mass spectra

Faculty conducting research in these areas:

  • Catherine Costello (Proteins, glycans and lipids)
  • Cheng Lin (Proteins, glycans)
  • Joseph Zaia (Glycosaminoglycans, protein-GAG interactions)

Development

Directed cell migration plays a critical role in embryonic development. To migrate in a directed way, a cell must be able to detect and move towards a source of an attractive signal (chemoattractant) or away from a repulsive one. This requires the creation of spatially asymmetrical signaling that leads to extension of leading edge protrusions such as lamellipodia, the generation of traction and force, and a balance of detachment and attachment to neighboring cells and the extracellular matrix. Thus, there is a constant need for the cell to coordinate a variety of extracellular and intracellular activities both spatially and temporally. The challenge is to understand how the cell compartmentalizes, yet cooperatively couples, these activities to drive directed cell movement and how upstream signaling controls this behavior. Toward this end, investigators in the Department of Biochemistry study growth factor signaling that is modulated by specific extracellular matrix proteins and induces specific changes in cellular architecture. In vivo and three-dimensional ex vivo models are studied in which growth factor signaling and downstream effectors are modulated through introduction of mutant forms, and resultant morphology and cell migration are analyzed.

Faculty conducting research in these areas:

  • Mikel Garcia-Marcos (G protein signaling)
  • Barbara M. Schreiber (Vascular development, ECM)
  • Vickery Trinkaus-Randall (EGF Receptor, glycosaminoglycans)
  • Bob Varelas (Development and cancer)

Student Life

Students are an important and integral part of any educational department and this is no different at BUSM’s Department of Biochemistry. In order to be more involved in departmental affairs, students of the department have created the Biochemistry Student Organization (BSO) to foster the academic and professional development of the student body. In addition to this primary mission, the BSO organizes and sponsors various social and academic events for students and the department. Our students are also active in the Division of Graduate Medical Sciences Student Organization (GMSSO), an organization that encompasses students in all programs throughout the Division of Graduate Medical Sciences.