Maryam Raeeszadeh-Sarmazdeh

Maryam Raeeszadeh-Sarmazdeh joined the University of Nevada, Reno in July 2019 as an assistant professor. Dr. Sarmazdeh was a senior research fellow in the Department of Cancer Biology at Mayo Clinic, Florida from 2017 to 2019 at Dr. Radisky’s lab, during which her work was focused on engineering novel protein-based therapeutics based on natural enzyme inhibitors. Prior to her appointment at Mayo Clinic, she was a postdoctoral scholar at the Chemical and Biomolecular Engineering Department at the University of Delaware at Prof. Wilfred Chen’s lab for 2.5 years. Dr. Sarmazdeh earned her Ph.D. in Chemical and Biomolecular Engineering from the University of Tennessee at Knoxville under Prof. Eric Boder’s supervision. There, her research was focused on generating site-specific protein immobilization on the surface and protein engineering using yeast surface display and directed evolution.

Iain Buxton

The Buxton lab is exploring contraction-relaxation coupling in the uterine myometrium in order to better understand and develop treatments for the problem of preterm labor. Preterm delivery of an underdeveloped fetus is a global problem. Babies delivered prior to full development at term have multiple medical problems that plague these individuals throughout their lifetime. Prematurity explains 75% of all fetal morbidity and mortality. Thus, beyond the tragic and costly fact of their prematurity, is the major impact on individuals and societies long-term. There are no effective (or FDA-approved) medications that prevent contractions of the uterus in patients who enter labor preterm (PTL). What is used is ineffective at allowing the fetus to remain in the womb until term. Drugs employed to prevent PTL (tocolytics) are only evaluated for an ability to prevent labor for 48 hours, a time during which treatments can ready the fetus to breath air. PTL leads to preterm delivery (PTD) in over 50% of cases. Spontaneous PTL (sPTL, no explanation such as infection) accounts for the majority of PTL.

The approach to sPTL we are pursuing is based on the non-canonical pathway by which NO relaxes myometrium. Our approach hypothesizes specific S-nitrosation differences in the protein fingerprint of sPTL compared with laboring myometrium. What is needed to investigate sPTL is to know the specific proteins that are post-translationally S-nitrosated and their abundance and/or unique presence and the impact of their S-nitrosation in pregnancy, labor and sPTL.

We have discovered particular unique proteins that are deferentially S-nitrosated and are pursuing their role in mediating relaxation on pregnancy and labor. One such protein is a channel called TREK-1. This channel is stretch-activated. We discovered genetic variants of the channel associated with PTL in women. Electrophysiological measurement of these gene variant channels suggests that their expression in women may constitute a mechanism to explain PTL in these patients. Drug discovery is in process to generate therapeutics to treat this form of PTL.

In a second thrust, the Buxton lab is looking for therapeutic targets in breast cancer. Tumor cells migrate to distant sites in the body before they are capable of forming aggressive metastases and thus remain dormant. We do not know the cellular behavior of disease we label latent but attracting a blood supply may be an early property that precedes and is required for those lesions that become malignant in women. Breast cancer specific mortality is almost exclusively a function of metastasis. Growth of tumor cells as metastases dictates that tumor cells must first develop a capillary blood supply or risk necrosis. Metastatic tumor cells have already attracted a blood supply, a hallmark of cancer. What activates dormant cells at metastatic sites to move from a quiescent to aggressive phenotype is not known. It is critical to determine the effect of a kinase we discovered to be released from cancer cells because every indication is that it produces a blood supply for cells that can later become malignant, an event that cannot take place unless a blood supply is available. Our current experiments are focused on the actions of the kinase that permit intravasation and extravasation of tumor cells that permit their passage to distant sites in the body where they can lodge and remain undetected for years. We have developed an inhibitor of the kinase and hope to demonstrate its potential a breast cancer prophylactic.

Ernesto Abel-Santos

Dr. Abel-Santos is interested in research that combines the areas of organic chemistry, biochemistry and microbiology. The Abel-Santos laboratory is currently applying enzymology approaches to the process of Bacillus spore germination. Due to its potential as a bioterrorism weapon, new methods to control B. anthracis (a.k.a ANTHRAX) infections are needed. B. anthracis spores are resistant to most type of antiseptic and antibiotic treatments. Although anthrax spores are resilient, they have to “taste” their environment to determine when conditions are right to germinate (e.g. your lungs) Using the information gathered from the kinetic models, we have developed nucleoside inhibitors against anthrax spore germination. These compounds have proven to be effective in protecting macrophage form anthrax-mediated killing.

Ronald Pardini

One of the most exciting projects in our laboratory is the investigation of the role of nutritional intervention in cancer therapy. We are demonstrating that different types and levels of dietary fat can slow tumor growth rates, increase tumor responsiveness to therapy, lower drug-host toxicity of certain anticancer agents, and reduce cachexia- the wasting syndrome associated with cancer victims. This research is working toward a nutritional-intervention clinical trial designed to improve the outcome of chemotherapy and patient well-being.  Our laboratory is also investigating the induction of oxidative stress by various chemicals in insects and cancer. More specifically we are investigating the biochemistry and molecular biology of antioxidant systems of insects and tumor cells in order to predict mechanisms of insect resistance to plant allelochemicals and other foreign chemicals. In addition, we are investigating the mechanisms of tumor cell resistance to pro-oxidant anti-cancer agents.  These projects have potential for the selective destruction of insect pests and the selective survival of specific plant species. We are utilizing our insect model system to predict oxidative stress from various xcuobiotics including environmental pollutants. In addition, this approach would predict a tumor cell’s sensitivity or resistance to pro-oxidant anti-tumor agents.