Anna Rodina, PhD

Senior Research Scientist
Lab Phone:
646-888-2216

My research in the Chiosis Laboratory has focused on the discovery and development of Heat Shock Protein 70 (Hsp70) inhibitors and on studying the role of heat shock proteins in cancer. I am using chemical tools designed and synthesized in the laboratory to identify proteins interacting with heat shock proteins or being affected by them in specific cancer cell settings and to elucidate mechanism associated with Hsp70 in cancers.

Recently, using 2,5’-thiodipyrimidine scaffold compounds computationally predicted by my colleagues to bind to a specific site of Hsp70, I have shown that a representative compound - YK5 - selectively interacted with Hsp70 and Hsc70, but not with the mitochondrial (Grp75) or the endoplasmic reticulum (Grp78) Hsp70 isoforms. My data indicated that YK5 inhibited Hsp70 functions in cancer cells by interfering with the oncogenic functions of the Hsp90/Hsp70 machinery. I have also shown that YK5 has no effect on HSF-1 activation, a feed-back effect thought to limit the potency of Hsp90 inhibitors. Currently, I and my colleagues are developing more potent Hsp70 inhibitors and are evaluating them in pre-clinical cancer models. Our ultimate goal is to translate these agents to clinic for the treatment of cancer patients.

Publications by Anna Rodina

Selected Publications

  1. Rodina A, Vilenchik M, Moulick K, Aguirre J, Kim J, Chiang A, Litz J, Clement C, Kang Y, She Y, Wu N, Felts S, Wipf P, Massague J, Jiang X, Brodsky J, Krystal G and Chiosis G. Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer. Nat Chem Biol 2007; 3(8):498-507.
  2. Luo W, Dou F, Rodina A, Chip S, Kim J, Zhao Q, Moulick K, Aguirre J, Wu N, Greengard P and Chiosis G. Roles of heat-shock protein 90 in maintaining and facilitating the neurodegenerative phenotype in tauopathies. PNAS 2007; 104(22):9511-9516.
  3. Moulick K, Ahn JH, Zong H, Rodina A, Cerchietti L, Gomes DaGama E, Caldas-Lopes E, Beebe K, Perna F, Hatzi K, Vu LP, Zhao X, Zatorska D, Taldone T, Smith-Jones P, Alpaugh M, Gross SS, Pillarsetty N, Ku T, Lewis JS, Larson SM, Levine R, Erdjument-Bromage H, Guzman M, Nimer SD, Melnick A, Neckers L, Chiosis G. Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90. Nature Chem Biol 2011, 7(11):818-26.
  4. Taldone T, Rodina A, Dagama Gomes EM, Riolo M, Patel HJ, Alonso-Sabadell R, Zatorska D, Patel MR, Kishinevsky S, Chiosis G. Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes. Beilstein J Org Chem. 2013 Mar 15;9:544-56.
  5. Rodina A, Patel PD, Kang Y, Patel Y, Baaklini I, Wong M, Taldone T, Yan P, Yang C, Maharaj R, Gozman A, Patel M, Patel H,  Erdjument-Bromage H, Talele T, Young JC and Chiosis G. Identification of an allosteric pocket on human Hsp70 reveals a novel mode of inhibition of this therapeutically important protein . Chemistry and Biology 2013, Dec 19;20(12):1469-80.

Patents

  1. Chiosis, Gabriela; Taldone, T.; Rodina, A.; Patel, P.; Kang, Y., Heat Shock Protein Binding Compounds, Compositions, and Methods for Making and Using Same, Memorial Sloan Kettering Cancer Center,  WO2011022440, February 24, 2011.
  2. Gabriela Chiosis, Tony Taldone, Anna Rodina, Pallav Patel, Yanlong Kang: Heat shock protein binding compounds, compositions, and methods for making and using same. Memorial Sloan Kettering Cancer Center. Oct, 4 2012: US20120252818.