Thesis title: "Biophysical and Pharmacological Characterization of Cytoplasmic Dynein Heavy Chain 1"
Graduation date: 2010
MBSB PhD Advisor: Dr. Billy W. Day
Hikmat's research in the MBSB program involved characterizing the structure of cytoplasmic dynein heavy chain 1 (>380 kDa) using a combination of chemical labeling, hydrogen/deuterium exchange mass spectrometry, and computational biology. Cytoplasmic dynein is an important motor protein that translocates in a retrograde manner along microtubules to transport various cargoes throughout the cell. Several of these cargoes have been associated with diseases including cancer, neurodegenerative diseases, and HIV, making cytoplasmic dynein an important target to study. Part of my research also involves identifying compounds that interact with cytoplasmic dynein to be used as inhibitors or activators. I have also done work investigating the use of biosensor surfaces (dual polarization interferometry and resonant mirror) to assemble microtubules and further characterize their interactions with microtubule-perturbing agents. Microtubules are responsible for several important functions including maintaining cell structure, signaling, and cell division, particularly during mitosis, by physically separating chromosomes and orienting the plane of cleavage. These roles are a function of microtubule dynamics, the relative rates of assembly and disassembly at both the plus and minus ends of the microtubules. Increased microtubule dynamics is a hallmark of cancer cells, which makes microtubules a target for several anti-tumor therapeutics.
Current location: Scientist with molecular services company Hematogenix, in Chicago.
Current email:
Education:
B.S. in Physics, Allegheny College (Aug. 2002. - May. 2006)
Ph. D. in Molecular Biophysics and Structural Biology Program, University of Pittsburgh, USA (2010)
Publications:
- Colombo R, Wang Z, Han J, Balachandran R, Daghestani HN, Camarco DP, Vogt A, Day BW, Mendel D, Wipf P. Total Synthesis and Biological Evaluation of Tubulysin Analogues. J Org Chem. 2016 in press
- Salum LB, Mascarello A, Canevarolo RR, Altei WF, Laranjeira AB, Neuenfeldt PD, Stumpf TR, Chiaradia-Delatorre LD, Vollmer LL, Daghestani HN, de Souza Melo CP, Silveira AB, Leal PC, Frederico MJ, do Nascimento LF, Santos AR, Andricopulo AD, Day BW, Yunes RA, Vogt A, Yunes JA, Nunes RJ. N-(1'-naphthyl)-3,4,5-trimethoxybenzohydrazide as microtubule destabilizer: Synthesis, cytotoxicity, inhibition of cell migration and in vivo activity against acute lymphoblastic leukemia. Eur J Med Chem. 2015;96:504-18
- Salum LB, Altei WF, Chiaradia LD, Cordeiro MN, Canevarolo RR, Melo CP, Winter E, Mattei B, Daghestani HN, Santos-Silva MC, Creczynski-Pasa TB, Yunes RA, Yunes JA, Andricopulo AD, Day BW, Nunes RJ, Vogt A. Cytotoxic 3,4,5-trimethoxychalcones as mitotic arresters and cell migration inhibitors. Eur J Med Chem. 2013 May;63:501-10
- Hikmat N. Daghestani, Guangyu, Zhu, Paul A. Johnston, Sunita N. Shinde, Jeffrey L. Brodsky, and Billy W. Day. Characterization of Inhibitors of Glucocorticoid Receptor Nuclear Translocation, a Model of Cytoplasmic Dynein-mediated Cargo Transport. Drug ASSAY Development and Technologies, 2012 Feb;10(1):46-60.
- Laura L. Vollmer, Maria Jiménez, Daniel P. Camarco, Wei Zhu, Hikmat N. Daghestani, Raghavan Balachandran, Celeste E. Reese, John S. Lazo, Neil A. Hukriede, Dennis P. Curran, Billy W. Day, and Andreas Vogt. A simplified synthesis of novel dictyostatin analogs with in vitro activity against epothilone B resistant cells and antiangiogenic activity in zebrafish embryos. Molecular Cancer Therapeutics, 2011, 10, 994-1006.
- Hikmat N. Daghestani and Billy W. Day. Theory and applications of surface plasmon resonance, resonant mirror, resonant waveguide grating, and dual polarization interferometry biosensors. Sensors, 2010, 10, 9630-9646.
- Hikmat N. Daghestani, David G. Fernig, and Billy W. Day. Evaluation of biosensor surfaces for the detection of microtubule perturbation. Biosensors and Bioelectronics, 2009, 25, 136-141.
