Tarmo Roosild, Ph.D.

Tarmo Roosild headshot

Tarmo Roosild, Ph.D.

Director, Structure-Guided Drug Discovery

Tarmo Roosild's Research Focus

Cancer, Cardiovascular Diseases, Diabetes - General, Neurological and Psychiatric Disorders, Structural Biology, Biochemistry
Antibiotic/Multidrug Resistance, Apoptosis and Cell Death, Bcl-2 Family, Cancer Biology, Cancer Metabolism, G-Protein Coupled Receptors, Kinase Inhibitors, Macromolecular Machines, Molecular Motors, Protein Structure-Function Relationships, Ligand-Mediated Protein Conformational Changes
X-Ray Crystallography, Drug Discovery, Biophysics, Chemical Biology, Fragment-Based Drug Design, High-Throughput/Robotic Screening, Ion Channels, Protein Engineering, Protein Structure Prediction, Protein-Small Molecule Interactions, Rational Drug Design, Biochemistry
Computational Modeling

Dr. Tarmo Roosild’s primary research focus at the Conrad Prebys Center for Chemical Genomics (Prebys Center) is to utilize high resolution structural biochemistry techniques and computational chemistry methods to expedite the translation of chemicals identified in screening experiments into highly efficacious and selective molecules that can be advanced as candidate therapeutics for the treatment of human disease. He supervises the activities of an experimental structural biology laboratory, which specializes in co crystallization of target proteins in complex with binding small molecules for the purpose of high resolution structural analysis through X-ray diffraction crystallography. He has extensive experience investigating ligand-mediated protein conformational switches and discerning the underlying dynamic mechanisms, knowledge of which is applicable toward designing effective activity modulators. Further, he has specialized in studying such processes in the context of membrane proteins and has produced patented new technology to facilitate the investigation of these pharmaceutically-critical targets. Additionally, Dr. Roosild’s group employs computational chemistry approaches and in silico methods for the purpose of improving ligand affinity and selectivity, as well as identifying new leads through virtual screening and molecular docking of compounds to target proteins of interest.
 

Structure-based DD


Currently active projects in Structure-Guided Drug Discovery are phosphatase inhibitors, which may provide new avenues for the treatment of diabetes; nuclear receptor antagonists, which potentially play a role in post-traumatic stress and other neurological disorders; and modulators of important metabolic enzymes, some of which are integral to the proliferation of malignant cancer cells.


Dr. Roosild interfaces closely with the Prebys Center’s Medicinal Chemistry unit to synergistically expedite the improvement of lead compounds toward viable drug candidates, and with the Assay Development as well as Protein Analysis groups to confirm the validity of and mechanisms of action underlying screening hits.

Tarmo Roosild's Bio

Dr. Tarmo Roosild is a structural biophysicist with over twenty years of experience in the elucidation and analysis of protein structure, having gained knowledge of X-ray crystallographic techniques in the laboratories of Dr. Wim Hol (University of Washington) and Dr. Senyon Choe (Salk Institute), NMR methods under the tutelage of Dr. Roland Riek (Salk Institute and ETH-Zürich), and membrane protein biophysics from Dr. Choe and Dr. Geoffrey Chang (UC San Diego). His research has produced high impact results within the fields of protein biophysics and biochemistry, as evidenced by first author publications in Science, PNAS, and Cell.

After a successful post-doctoral tenure, culminating in patented new technology for the recombinant production of human membrane proteins, Dr. Roosild joined the newly-founded Nevada Cancer Institute (NVCI) as a junior faculty member, forming the first successful research unit for the determination of protein structure at high resolution within the state of Nevada. His lab focused on the structure-guided development of novel small molecule drugs, specifically for the oncologic rescue of fluorpyrimidine chemotherapeutic agents through modulation of uridine phophorylase activity. Additional drug discovery projects focused on elucidating the mechanism of action for a novel class of pathogen antibiotics and rational improvement of a Sirtuin 3-selective inhibitor of the protein’s deacetylation activity.

In November of 2015, Dr. Roosild joined SBP as Director of Structure-Guided Drug Discovery to lead efforts in both structural biology and computational chemistry supporting the mission of the Conrad Prebys Center for Chemical Genomics. His role includes supervising experimental wet-lab research aimed at determining rational strategies toward optimizing the chemical design of potential novel therapeutics. His group also engages in computational analysis of target protein structures to uncover new approaches toward beneficially modulating their behavior for the treatment of human maladies.

Roosild cell image

Publications

Roosild TP, Greenwald J, Vega M, Castronovo S, Riek R, Choe S
Science 2005 Feb 25;307(5713):1317-21
Roosild TP, Castronovo S, Healy J, Miller S, Pliotas C, Rasmussen T, Bartlett W, Conway SJ, Booth IR
Proc Natl Acad Sci U S A 2010 Nov 16;107(46):19784-9
Roosild TP, Castronovo S, Villoso A, Ziemba A, Pizzorno G
J Struct Biol 2011 Nov;176(2):229-37
Roosild TP, Castronovo S, Healy J, Miller S, Pliotas C, Rasmussen T, Bartlett W, Conway SJ, Booth IR
Proc Natl Acad Sci U S A 2010 Nov 16;107(46):19784-9
Roosild TP, Castronovo S
PLoS One 2010 Sep 14;5(9):e12741