Nicholas Borotto

My research program strives to improve mass spectrometric-based detection and analysis of biomolecules. In particular, we pair mass spectrometry with chemical derivatization, photon irradiation, ion mobility, and radical chemistry to elucidate the three-dimensional structure of proteins, better characterize the acidic and hydrophobic proteome, detect and localize post-translational modifications. Centered at the interface of chemistry and biology, my research program provides students with the opportunity to tackle both biochemically-focused projects and biophysical questions at the core of the techniques themselves. Currently, my group is recruiting students for three projects:

1) Equipping a carbon monoxide laser to a mass spectrometer, characterizing the behavior of irradiated biomolecules, and applying infrared multiphoton dissociation (IRMPD) to instruments and at pressure regimes traditionally precluded from this technique.

2) Probing protein three-dimensional structure with photocaged small molecule reagents both in vitro and in vivo and demonstrating the utility of the temporal and spatial control that is provided by these probes.

3) Applying the tandem mass spectrometry technique free-radical initiated peptide sequencing (FRIPS) to complex mixtures of anions.

Steve Frese

Dr. Frese’s research is centered on the human gut microbiome and its inhabitants. Our work at the University of Nevada, Reno examines how diet, food science, and biotechnology can be leveraged to meaningfully improve human health and nutrition.

Monika Gulia-Nuss

The long-term interest of my research program is to understand the biology of disease vectors to identify novel strategies for vector control and pathogen transmission. My lab focuses on two arthropod vectors of human diseases: mosquitoes and ticks. Our research spans multiple disciplines, including ecology, biochemistry and physiology, genetics, genomics, and computational biology, to investigate questions related to arthropod biology. We employ techniques that encompass molecular, cellular, and organismal levels of studies. Since setting up my lab at UNR in 2016, the most significant research contributions of my program have been 1) pioneering an embryo injection protocol for ticks, 2) the first successful use of CRISPR/Cas9-based genome editing in ticks, 3) producing the first chromosome-level genome assembly for a tick species, and 4) adapting and optimizing a RADseq protocol (Rapture) for genome-wide markers to understand population genetic structure of mosquitoes and ticks. In addition, we have recently initiated a project for the identification of biomarkers for early diagnostics of Lyme disease.

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.