Research Interests: The Hinck lab uses structural and biophysical tools (NMR, X-ray crystallography, SPR, ITC, etc.) to study the signaling proteins and receptors of the TGF-β family. TGF-β plays important physiologic and pathogenic roles, being implicated in immune regulation, cell proliferation/differentiation, and cancer progression. My research aims to characterize a parasitic TGF-β mimic that binds to the type 1 and type 2 TGF-β receptors (TβRI and TβRII) by characterizing the structure of this mimic and analyzing its binding interfaces with TβRI and TβRII. I use a combination of biochemical techniques, NMR, and ITC/SPR experiments.
B.A. in Biophysics, University of Michigan, 2016
PhD Advisor: Dr. Andrew P. Hinck
email: anm276 [at] pitt.edu
My work involves expanding the genetic code of zebrafish to incorporate unnatural amino acids into proteins of interest. I have used this technology to optically control enzymes by installing photolabile groups into the active site. Additionally, I am developing a phosphine-triggered protein activation method by placing aryl-azide caged lysine into enzymes. I am also developing a method for incorporation of chemically diverse residues into proteins in zebrafish through injection of chemically acylated tRNA. Aside from genetic code expansion, I am generating optically-controlled CRISPR-based tools in zebrafish and light-activated morpholino oligonucleotide gene knockdown.
B.S in Bioresource Research, B.A in International Studies, 2016, Oregon State University
PhD Advisor: Dr. Alexander Deiters
Chevron Science Center
219 Parkman Ave, Pittsburgh, PA
Zhou W, Brown W, Bardhan A, Delaney M, Ilk AS, Rauen RR, Kahn SI, Tsang M, Deiters A. Spatiotemporal Control of CRISPR/Cas9 Function in Cells and Zebrafish using Light-Activated Guide RNA. Angew. Chem. Int. Ed. 2020 , 59 , 8998.
Brown W, Deiters A. Light-activation of Cre recombinase in zebrafish embryos through genetic code expansion. Methods Enzymol. 2019;624:Ch. 13
3) Brown W, Liu J, Deiters A. Genetic Code Expansion in Animals. ACS chem biol. 2018;13(9):2375-86
Brown W, Liu J., Tsang M., Deiters A.; Cell‐Lineage Tracing in Zebrafish Embryos with an Expanded Genetic Code, ChemBioChem, 27 April 2018, Vol.19(12), 1244-1249
Bednar R, Golbek T, Kean K, Brown W, Jana S, Baio J, Karplus PA, Mehl R. Immobilization of Proteins with Controlled Load and Orientation, ACS Appl. Mater. Interfaces 2019, 11, 40, 36391-36398
Blizzard RJ, Backus DR, Brown W, Bazewicz CG, Li Y, Mehl RA. Ideal Bioorthogonal Reactions Using A Site-Specifically Encoded Tetrazine Amino Acid. J Am Chem Soc. 2015;137(32):10044-7
Brown W., Zhou W., and Deiters A., Regulating CRISPR/Cas9 Function through Conditional Guide RNA Control, Chembiochem, 2020 (submitted)
Erich Hellemann Holguin
Research Interests: My background is in the use of anisotropic NMR parameters for the structural elucidation of small organic molecules. Currently, my research interests focus on computer-aided drug discovery, virtual screening, molecular dynamics simulations, and weighted ensemble path sampling.
B.S. in Chemistry, Universidad Nacional Autónoma de México, Ciudad de México, 2011
M. S. in Chemistry, Carnegie Mellon University, Pittsburgh, PA, 2016
PhD Advisor: Dr. Jacob Durrant
103 Clapp Hall
4249 Fifth Ave
Pittsburgh, PA 15260
email: ehellemann [at] pitt.edu
- Hellemann E., Gil RR New stretching method for aligning gels. Its application to the measurement Residual Chemical Shift Anisotropies (RCSAs) without the need for isotropic shift correction. Chemistry. 2018, 24(15), 3689-93
- Hallwass F, Teles RR, Hellemann E, Griesinger C, Gil RR, Navarro-Vazquez A. Measurement of residual chemical shift anisotropies in compressed PMMA gels. Automatic compensation of gel isotropic shift contribution. Magn Reson Chem. 2018 in press
- Waratchareeyakul W, Hellemann E, Gil RR, Chantrapromma K, Langat MK, Mulholland DA. Application of Residual Dipolar Couplings and Selective Quantitative NOE to Establish the Structures of Tetranortriterpenoids from Xylocarpus rumphii (Meliaceae). J Nat Prod, 2017, 80 (2), 391–402.
- Hellemann E, Teles RR, Hallwass F, Barros Jr. W, Navarro-Vázquez A, Gil RR, Mechanical behavior of polymer gels for RDCs and RCSAs collection. NMR imaging study of buckling phenomena, CHEM-EUR J, 2016, 22 (46), 16632–16635.
- Castañar L, García M, Hellemann E, Nolis P, Gil RR, Parella T, Efficient structure discrimination by fast and accurate measurement of residual dipolar couplings from a single experiment in PMMA compressed gels, J Org Chem, 2016, 81 (22), pp 11126–11131.
- García ME, Woodruff SR, Hellemann E, Tsarevsky NV, Gil RR, Di(ethylene glycol) methyl ether methacrylate (DEGMEMA)-derived gels align small organic molecules in methanol, Magn Reson Chem, 2017, 55 (3), 206-209.
Worch JC, Hellemann E, Pros G, Gayathri C, Pintauer T, Gil RR, Noonan KJT, Stability and Reactivity of 1,3-Benzothiaphosphole: Metallation and Diels-Alder Chemistry, Organometallics, 2015, 34 (22), 5366–5373.
Yuri Kochnev, Erich Hellemann, Kevin C Cassidy, Jacob D Durrant, Webina: An Open-Source Library and Web App that Runs AutoDock Vina Entirely in the Web Browser, Bioinformatics, , btaa579, https://doi.org/10.1093/bioinformatics/btaa579
I am interested in the structure and function of nucleic acids and the proteins that bind to and act on them. In the Opresko lab, my research focuses on nucleic acid structures that form within the telomere and how they influence interactions with telomerase. I am also part of a collaboration that aims to understand the structure and function of human telomerase.
B.S. in Chemistry with a Specialization in Biochemistry; University of Virginia (Charlottesville, VA), May 2017
PhD Advisor: Dr. Patricia Opresko
Hillman Cancer Center,
Research Pavilion Lab 2.1,
5117 Centre Ave. Pittsburgh, PA 15213
email: saj98 [at] pitt.edu
- Morgan RD, Luyten YA, Johnson SA, Clough EM, Clark TA, Roberts RJ. Novel m4C modification in type I restriction-modification systems. Nucleic Acids Res. 2016 Nov 2; 44(19): 9413-9425
Schaich MA, Sanford SL, Welfer GA, Johnson SA, Khoang TH, Opresko PL, & Freudenthal BD. (2020) Mechanisms of nucleotide selection by telomerase. eLife, 9:e55438. DOI: 10.7554/eLife.55438. [PubMed: 32501800]
My research is centered around (1) the development of Cu(II)-based site-directed spin-labeling (SDSL) for Electron Paramagnetic Resonance (EPR)-based distance measurements and (2) applying these techniques to answer fundamental questions about protein-DNA interactions. SDSL methodologies allow for the incorporation of stable unpaired electrons at specific sites of a protein or DNA. When two or more unpaired electrons are incorporated, EPR can measure the distance between the two unpaired electrons with angstrom resolution. Additionally, these measurements are crucial for studying protein systems that are too large for NMR-based experiments or too complicated to be crystallized for X-ray crystallography.
Our group has pioneered Cu(II)-based SDSL that are rigid and small. As a result, the Cu(II) distances primarily reflect the motions of protein or DNA in solution. These distances allow for observation of conformational changes and elucidate the assembly of large oligomers. Specifically, I use distance measurements to observe protein-DNA interactions in solution to shed light on structural principles that govern highly-specific sequence-specific DNA recognition.
Education: BA, Biochemistry, University of Montana, 2017
PhD Advisor: Dr. Sunil Saxena
Department of Chemistry
723 Chevron Science Center
219 Parkman Ave
Pittsburgh, PA 15260
email: ZIH12 [at] pitt.edu