School of Medicine

Wayne State University School of Medicine

Research Programs

Research interests in the Department of Biochemistry and Molecular Biology are diverse, allowing graduate students to choose from a broad spectrum of topics when picking a research lab. Regular interactions between students and faculty are facilitated with weekly departmental and student seminars, formal collaborations between research groups and a cooperative work environment that promotes discussion of research projects between students of different labs. Programs that cover the research performed in this department are described in detail below.

1. Structural Biology(Edwards, Gatti, Kovari, Stemmler, Wang, Yang)
Structural biology provides the framework for understanding how biomolecules function. The X-ray crystallographic component of the departmental Structural Biology program is at the leading edge in this field. The Wayne State’s Advanced Laboratory for Macromolecular Crystallography (ALMC), located in our department, is one of few laboratories in the world that possesses a high-flux X-ray generator capable of producing an X-ray beam that is 5 times stronger than conventional generators. Our department also participates in a state-funded program for developing a $13 million X-ray diffraction station at the Advanced Photon Source (APS) at the Argonne National Laboratories in Chicago. Research in the field of Nuclear magnetic resonance spectroscopy (NMR) provides a second component of our department’s Structural Biology program. The department has an impressive arsenal of NMR spectrometers at our disposal, providing students access to a 700 MHz, 600 MHz, 500 MHz and 400 MHz spectrometers (most with cryoprobes) for their research. In addition, the department participates in a state-funded program that allowed the recent purchase of a 900 MHz spectrometer, which will be located close to our university and available for our students to use. Current projects in the field of structural biology include:

  • Regulation of mammalian blood clotting proteins.
  • Metal and metalloid homeostasis regulation and transport proteins.
  • Bacterial cell wall development.
  • HIV-1 viral maturation events.
  • Proteins that confer antibiotic resistance in bacteria.
  • Flavoenzyme structure and function.
  • Structural characterization of chaperones.
  • Structure and function of histone methyltransferase in heart diseases

2. Cellular Metal Homeostasis and Drug Resistance
 (Akins, Bhattacharjee, Edwards, Evans, Kovari, Lee, Lightbody, Mitra, Mukhopadhyay, Rosen, Stemmler, Vinogradov)
Cells have evolved pathways to control metal homeostasis and drug resistance in an attempt to maintain viability under normal and stress induced conditions. If one possesses a general understanding of these events, and the proteins that influence them, we can control dysfunctional processes in humans that lead to a variety of disorders. Research in these areas within our department include:

  • Metal influx and efflux transporters, chaperones and the P-type ATPases.
  • Mechanisms of transport and detoxification of metals and metalloids.
  • Control of cellular oxidative stress.
  • Heme and iron-sulfur cluster biosynthesis.
  • Drug resistance conferred by HIV-1 protease mutants.
  • Antibiotic resistance in gram-negative bacteria.
  • Pathogenic fungal drug resistance mechanisms.
  • Biochemical basis of immunodeficiency diseases.

3. Molecular Biology and Cancer (Brooks, Edwards, Evans, Finley, Johnson, Needleman)
Cancer is a major global health problem that prevents a large number of humans from living a normal and healthy life. Disruption of normal homeostatic pathways leads to aberrant behavior in cells and this is at the heart of cancer. To make progress in fighting cancer, we must learn how cellular processes are regulated. Molecular biology is central to this enterprise, and it is the focus of a number of research groups in the Department. Research in molecular biology is ongoing in our department in the following areas:

  • Estrogen receptor regulation of gene transcription.
  • DNA synthesis pathways.
  • Mitochondrial genetics.
  • Cell cycle regulation pathways.
  • Phosphorus chemistry.
  • Regulation of gene transcription.
  • Regulation of expression of ATPase genes.
  • Relationship between gene expression and the assembly and activity of F-ATPase.

4. Molecular and Cellular Bioenergetics
 (Ackerman, Brusilow, Edwards, Gatti, Lee)
Mitochondria are the source of metabolic energy for nearly all cellular activities. These complex organelles comprise proteins coded by their own genomes and by the nuclear genome, as well as a diverse array of complex lipids. The way in which the components are assembled into a functional unit remains a major question. The details of energy transduction via electron transfer remain an enigma, whose solution would yield a profound insight into one of the most significant components of eukaryotic metabolism. Finally, mitochondria play the major role in initiating apoptotic cell death, with enormous implications for embryonic development, central nervous system architecture and cancer. Current projects being carried out by researchers in the Department of Biochemistry and Molecular Biology include:

  • Mitochondrial ATP synthase assembly.
  • Structure and function of the E. coli proton-translocating ATPase/ATP synthase.
  • Proteins involved in energy transduction in bacterial and eukaryotic membranes.
  • Mitochondrial bioenergetics.

5. Enzymology (Evans, Edwards Gatti, Mitra)
Nearly all of the metabolic activities that make up the life of the cell are carried out by proteins - enzymes and transport proteins. Enzymes catalyze an astonishing and diverse range of chemical transformations. A second set of important functional proteins are the membrane proteins that transfer molecules in and out of the cell. In addition to elucidating the biological activity of these proteins, researchers in the Department are also interested in the chemical mechanisms that they utilize to carry out this diverse array of activities. Some projects now in progress include:

  • The multifunctional enzymes of pyrimidine biosynthesis.
  • Thermophilic enzymes.
  • Structure and mechanism of oxidative enzymes.
  • Mechanisms of reactions catalyzed by flavoproteins.
  • Molecular mechanisms of transport of soft metals and metalloids.
  • Heavy metal detoxification (arsenic, lead, and other metals).