Introducing Our Authors pubs.acs.org/acschemicalbiology
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NICOLE RAMSEY
Education. Moscow State University, M.S. in Microbiology; Blokhin’s Cancer Research Center, Ph. D. in Cancer Biology; Colorado University Health Sciences Center, Research Fellow, Cancer Research with Dr. Irina Budunova; New York University Medical Center, Research Associate, Biochemistry with Prof. Nigel Godson; Memorial Sloan Kettering Cancer Center, Postdoctoral research fellow, Drug Discovery and Chemical Biology with Prof. Gabriela Chiosis Nonscientific Interests. Movies, traveling My research interests are focused on studying heat shock proteins in transformed systems. Evidence accumulated in recent years suggests that the role of heat shock proteins (mainly Hsp90 and Hsp70) in cancer is quite different from their function in normal cells. In cancer cells, heat shock protein complexes support functional conformation of wide variety of onco-proteins involved in control of cell growth, differentiation, and survival. Identification of such oncoproteins in specific tumors would allow development of rational treatment strategies. As described in our paper, we have developed a chemical tool to analyze Hsp70-regulated proteome. It is based on a novel Hsp70 inhibitor, YK5, discovered in the laboratory. The tool has an ability to lock Hsp70 in the complex with onco-client proteins and, as a result, allows effective isolation of Hsp70 complexes, which can be further identified. This provides valuable information to dissect tumor specific roles of Hsp70. (Read Rodina’s article, DOI: 10.1021/cb500256u)
Image courtesy of Ruth Gotigan. Education. Howard University, B.S. in Biology, 2007; Weill Cornell Graduate School in Biomedical Sciences, Ph.D. in Pharmacology, 2014; Weill Cornell Medical College, M.D. pending in 2015, Research Advisor: Dr. Olaf Andersen, M.D. Nonscientific Interests. Pilates, theater, travel, mentoring, diversity in science and medicine My current interests include translational research that is aligned with my clinical interests in pediatric infectious disease and critical care, particularly related to new pharmacotherapies and protocols related thereto. My thesis work focused on the offtarget effects of drugs on lipid bilayers, particularly antimalarial drug candidates and cAMP pathway modifying compounds. I also contributed to a project that identified a new potential drug target for antimalarial drug discovery. This paper is the product of a multi-institution and multi-disciplinary collaboration that focuses on the way that phytochemicals (including resveratrol and ECGC) affect lipid bilayers by altering the properties of membrane proteins. The results are particularly intriguing when one considers how their varied membrane protein or intracellular protein targets might be influenced by their effects on lipid bilayers. (Read Ramsey’s article, DOI: 10.1021/cb500086e)
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SUSHABHAN SADHUKHAN
ANNA RODINA
Image courtesy of Mintu Porel.
Current Position. Cornell University, Ithaca, NY, Department of Chemistry and Chemical Biology, Postdoctoral Researcher with Prof. Hening Lin since September 2012 Education. University of Calcutta, India, B.Sc. in Chemistry, 2005; Indian Institute of Technology Delhi, India, M.Sc. in Chemistry, 2007; Case Western Reserve University, USA, Ph.D. in Chemistry, 2012, with Prof. Gregory P. Tochtrop; Cornell University, Postdoctoral Research with Prof. Hening Lin since September 2012
Image courtesy of Henry S. Balingcongan. Current Position. Senior Research Scientist, Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center © 2014 American Chemical Society
Published: August 15, 2014 1639
dx.doi.org/10.1021/cb500615e | ACS Chem. Biol. 2014, 9, 1639−1640
ACS Chemical Biology
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Nonscientific Interests. Cricket, cooking, spending time with friends and family The central tenet of my Ph.D. work revolved around the metabolomics study of an interesting class of molecules, 4-hydroxyacids. These molecules can be produced endogenously, such as with 4-hydroxy-2-(E)-nonenal (4-HNE), which is derived from the lipid peroxidation. Alternatively they can come from exogenous sources, such as drugs of abuse including γ-hydroxybutyric acid (GHB) and γ-hydroxypentanoic acid (GHP). With the combination of mass-isotopomer analysis and metabolomics, we have discovered the catabolic pathways of 4-HNE, GHP, and GHB. In this article, we report a metabolomics study revealing the biochemical fate of GHB using various 13C incorporation labeling patterns. I believe this comprehensive study of the metabolic fates of GHB will increase our understanding on a compound that is used (and abused) as much as GHB. (Read Sadhukhan‘s article, DOI: 10.1021/cb500380b)
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Introducing Our Authors
TONY TALDONE
Image courtesy of Mohammad Uddin.
Current Position. Senior Research Scientist at Memorial SloanKettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, New York Education. St. John’s University, BS, Chemistry; St. John’s University, MS in chemistry with Prof. István Lengyel and Prof. Victor Cesare; St. John’s University, Ph.D. in Medicinal Chemistry with Prof. S. W. Zito; Postdoctoral research fellow, drug development and chemical biology, with Prof. Gabriela Chiosis Nonscientific Interests. Reading, traveling, spending time with friends and family, watching soccer, football and baseball My research interests lie in the development of small molecule probes designed to study the role of aberrant chaperone function in cancer cells and furthermore to develop drugs that exploit the dependence that cancer cells have for these chaperones. My focus in these endeavors has been on the heat shock proteins (Hsp) Hsp90 and Hsp70. Hsp90 has proven to be a relatively druggable target, and numerous ATP-competitive ligands are known that target the nucleotide binding pocket. Drug development efforts have led to approximately 20 compounds that have entered into clinical evaluation for various types of cancer. In contrast, it has been much more difficult to identify potent and selective inhibitors of Hsp70. We believe that Hsp70 is a viable anticancer target and represents the next frontier in the development of drugs targeting aberrant chaperone function. In this paper, we describe our efforts at developing tool molecules based on the novel Hsp70 inhibitor YK5. YK5 is an irreversible inhibitor that targets a cysteine residue located in an allosteric pocket in the ADP conformation of Hsp70. Here we show that a biotinylated analogue of YK5 is able to trap Hsp70 in an ADP conformation bound to the activating cochaperone Hsp110 and onco-proteins in cancer cells and in lysates. Since this tool molecule can lock Hsp70 in complex with onco-proteins, it can enable study of the Hsp70-interactome in cancer cells and in so doing can allow for a detailed analysis of Hsp70 binding partners in a tumor-by-tumor manner. As such, biotinylated YK5 can serve to enhance our knowledge on the tumor -specific roles of Hsp70. We are currently developing Hsp70 inhibitors for in vivo use with the full hope that such compounds will enter clinical evaluation. We are in the beginning steps of a journey that we hope leads to clinically viable Hsp70 inhibitors that can benefit cancer patients. (Read Taldone’s article, DOI: 10.1021/ cb500256u)
ASHWANI K. SHARMA
Image courtesy of Ashwani K. Sharma.
Current Position. University of Kentucky, College of Pharmacy, Postdoctoral Fellow with Prof. Peixuan Guo Education. Guru Nanak Dev University, India, M.Sc. in Chemistry, 2003, Advisor: Prof. Mohinder P. Mahajan; National Chemical Laboratory, India, Ph.D in Chemistry, 2010, Advisor: Prof. Krishna N. Ganesh; University of Utah, Department of Chemistry, Postdoctoral Fellow 2011−2013, Advisor: Prof. Jennifer M. Heemstra Nonscientific Interests. Music, story-writing, videography and cooking My research interests include exploring nucleic acids beyond their role in biology’s central dogma, evolving them as molecular recognition entities to sense specific targets or act as catalysts to direct chemical transformations. My recent work in the Heemstra lab focused on developing a method to fluorescently label specific RNA sequences using a selfalkylating ribozyme that we generated via in vitro selection. The evolved RNA sequence reacts selectively with a functionalized fluorescein analogue, promoting covalent attachment of the fluorophore to the RNA. We anticipate that this work will have significant utility for in vitro labeling of specific RNA sequences and may provide a new approach to labeling and imaging RNA in live cells. Read (Sharma’s article, DOI: 10.1021/cb5002119) 1640
dx.doi.org/10.1021/cb500615e | ACS Chem. Biol. 2014, 9, 1639−1640
