Faculty - J. MICHAEL MULLINS

J. MICHAEL MULLINS Professor

Phone: (202) 319-5279 FAX: (202) 319-5721 e-mail: mullinsj@cua.edu

EDUCATION AND TRAINING:

Ph.D., Cell Biology, University of Texas at Austin

Post-Doctoral Research, Dept. of Molecular, Cellular, and Developmental Biology, University of Colorado

TEACHING INTERESTS:

Introductory Biology

Cell Structure and Function

Physiology

RESEARCH INTERESTS:

The major focus of my laboratory is that of biological effects that are induced by weak, electromagnetic (EM) fields. This area of research has received considerable attention, and controversy, as the result of epidemiologic data which indicated that exposure to 60 Hz electromagnetic fields may produce a two-fold or greater increase in the incidence of childhood leukemia, malignant brain tumors, and some other cancers. Since 50-60 Hz EM fields are ubiquitous in modern society, it is important to understand how cells detect and respond to them. The interdisciplinary research team of which I am part has demonstrated definite effects of weak, 60 Hz electromagnetic fields on the development of chicken embryos, and on specific enzyme activities in both chicken embryos and cultured mammalian cells. We have explored the mechanism by which cells detect such fields, and used this information to devise means to inhibit or prevent their detection.

In addition to their possible harmful effects, however, EM fields also offer the potential for promoting beneficial effects. The clinically approved use of EM fields to enhance the knitting of broken bones that otherwise fail to heal is a good example of a field-induced, beneficial effect.  Our current research is focused on the potential of using EM field exposure to protect cells against the damaging effects that occur when cells are subjected to hypoxia, followed by reoxygenation.  Our research group originally showed that in ovo, EM field exposure of chicken embryos nearly doubled their rate of survival when they were subsequently placed under hypoxic conditions and then reoxygenated.  We have now extended this observation to a set of experiments in which cell cultures serve as a model system to investigate the effects of EM fields on simulated heart attack, followed by reperfusion.  Cultures of H9c2 cells, derived from embryonic rat heart, are subjected to hypoxia coupled with nutrient deprivation to simulate the effects of ischemia.   Reperfusion is then simulated by providing the cells normal growth medium to supply nutrients, such as glucose, and restoring normal oxygen levels.  EM field exposure prior to the onset of hypoxia results in a 40-50% increase in cell survival compared to that of matched, unexposed control cultures.  This is probably the result of induction or augmentation of specific, signal transduction pathways in cells exposed to the field.  The increased survival with EM field exposure correlates with enhanced levels of the HO-1 stress protein, but not that of Hsp72.  Additionally, levels of the BCl2 protein, that prevents apoptosis (programmed cell death), are enhanced in field-exposed cells, and caspase enzyme activity, which accomplishes apoptosis, is diminished.  Thus, a major factor in field-induced cell survival appears to be a decrease in apoptotic activity.  This work is ongoing.

An additional project underway in my laboratory is centered on the effects of the neurotoxin acrylamide.  The mechanism by which acrylamide exerts its toxic effects is not understood.  We discovered, however, that it affects the ability of mammalian, cultured cells to adhere to their growth surface. Acrylamide greatly diminishes cell adhesion, simultaneously disrupting the network of actin-based stress fibers and focal adhesions in the cells. This disruption causes the cell to lose attachement and become round, eventually resulting in cell death. The deleterious effects of acrylamide exposure can be countered by raising the cytoplasmic level of cyclic AMP. We are currently investigating the mechanisms by which cyclic AMP blocks acrylamide-induced loss of cell adhesion. These studies involve a combination of microscopy, immunocytochemistry, immunochemistry, and biochemistry. Recent results show that the phosphorylation state of some of some focal adhesion proteins is altered by acrylamide, but that the normal phosphorylation state can be maintained if cyclic AMP is applied simultaneously with acrylamide. We believe that studies such as these will be useful for furthering understanding not only the mechanism by which the toxicity of agents such as acrylamide is achieved, but will also provide a better understanding of the mechanisms that provide for normal cell adhesion and functioning.

RESEARCH FUNDING:

Research on the biological effects of EM fields has received funding from the Department of the Army, N.I.E.H.S., and through venture capital investments.

RECENT PUBLICATIONS:

1. A.L. Di Carlo, J.M. Mullins, and T. A. Litovitz. 2000. Electromagnetic field-induced protection of chick embryos from hypoxia exhibits characteristics of temporal sensing. Bioelectrochemistry, 52:17-21.
2. A.L. Di Carlo J.M. Mullins, and T. A. Litovitz. 2000. Thresholds for EM field-induced hypoxia protection: evidence for a primary, electric field effect. Bioelectrochemistry, 52:9-16.
3. Kurian, M.V., J. M. Mullins, L. R. Hamilton, P. M. Mehl and J. K. Keevan. 2006.  Elevated levels of stress proteins (Hsp32 and Hsp70i) in H9c2 cells exposed to 60 Hz, 120 μT magnetic field.  Molecular & Cellular Biomechanics.  3:217-218.
4. Rutledge, R., M. Ghistain, J.M. Mullins, C. Pety de Thozée, and J. Golin. 2008. Pdr5-mediated multidrug resistance requires the CPY-vacuolar sorting protein Vps3: Are xenobiotic compounds routed from the vacuole to plasma membrane transporters for efflux?    Molecular Genetics and Genomics, 279:573-583.