Dennis Liotta, Ph.D.
Samuel Candler Dobbs Professor of Chemistry Executive Director, Emory Institute for Drug Development
|Ph.D.||The City Univ. of New York||New York||1974|
|B.A. Chemistry||Queens College||Queens, NY||1970|
- Post-doctoral Experience
- Postdoc, Organic Chemistry, The Ohio State University, 1974-1976
- Honors and Awards
- ACS Smissman Award (2015)
Fellow, Australian Academy of Technological Sciences and Engineering (2014)
Fellow, National Academy of Inventors (2013)
Uncommon Courage Award, Queens College (2012)
Thomas Jefferson Award, Emory University (2011)
Fellow, American Chemical Society (2010-present)
ACS Medicinal Chemistry Hall of Fame (2010)
Herty Award (2005)
- Research Interests
- The Liotta laboratory is primarily interested in the identification and development of novel antiviral, anticancer and anti-inflammatory therapeutics. Efforts are currently focused in three major areas: (a) the development of small molecule modulators of the chemokine receptor, CXCR4; (b) the development of small molecule NMDA receptor antagonists and potentiators; and (c) the development of novel nucleoside analogs as potential inhibitors of a wide range of DNA and RNA viral polymerases.
CXCR4: The CXCR4 receptor plays an important role in a wide range of human disease pathologies, such as X4-tropic HIV-1 entry, inflammation and cancer metastasis. The interaction between CXCR4 and its natural ligand, CXCL12, also synchronizes many essential physiological roles, such as homeostatic regulation of leukocyte trafficking, hematopoiesis and embryonic development. The complexity of the many signaling pathways associated with this receptor makes it very challenging to develop safe and effective modulators of it. This notwithstanding, they have recently identified a variety of agents that, as a consequence of their different binding modes, selectively modulate different functions of the receptor. As one example of this, the research group has recently discovered a series of potent, dual tropic (CCR5/CXCR4) HIV entry inhibitors.
NMDA: Glutamatergic neurotransmission through ionotropic-glutamate receptors is the primary means of excitatory synaptic transmission in the mammalian central nervous system (CNS). The receptor family comprises the -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), N-methyl-D-aspartate (NMDA) and kainate receptors. NMDA receptors are widely expressed in the CNS and are thought to be involved in a range of important physiological processes including axonal guidance, synaptic plasticity and memory formation. NMDA receptors are also thought to play an important role in pathophysiological conditions, including Parkinsonís disease, schizophrenia, depression, and ischemia.
The spatially-restricted expression patterns, together with distinct functional and pharmacological differences imparted by the GluN2 subunits, make NMDA receptor subunit-selective modulators of therapeutic interest for several neurological disorders, including stroke, schizophrenia, treatment-resistant depression and Parkinsonís disease. Subunit-selectivity will restrict modulator actions to brain regions that express the subunit of interest, potentially limiting side effects that occur as a result of global NMDA receptor blockade.
Nucleoside Analogs: Viral polymerases play an essential role in viral replication and, as a consequence, their inhibition has proven to be a viable strategy for controlling a wide variety of viral infections. In the Liotta group, we design and test new nucleoside and nucleotide analogues with the aim of developing antiviral drugs that can address many important unmet medical needs that include, inter alia, Dengue fever, Venezuelan equine encephalitis, hepatitis B and C and respiratory syncytial virus. As one example on this, they, in collaboration with colleagues at the Emory Institute for Drug Development, have identified a novel nucleoside analogue, EIDD-2023, for treating hepatitis C infections.
- Representative Publications
- An Orally Available, Small-Molecule Polymerase Inhibitor Shows Efficacy Against a Lethal Morbillivirus Infection in a Large Animal Model. Sci. Transl. Med. 2014, 6(232), p. 232ra52. Krumm S. A.; Yan, D.; Hovingh, E.; Evers, T. J.; Enkirch, T.; Prabhakar R.; Sun, A.; Manohar T.; Arrendale, R.; Painter, G.; Liotta, D.; Natchus, M.; von Messling, V.; Plemper, R.
Design, Synthesis, and StructureĖActivity Relationship of a Novel Series of GluN2C-Selective Potentiators. J. Med. Chem. 2014, 57 (6), 2334-2356. Zimmerman, S. S.; Khatri, A.; Garnier-Amblard, E.C.; Mullasseril, P.; Kurtkaya, N.L.; Gyoneva, S.; Hansen, K.B.; TrayneliS, S. F.; Liotta, D. C.
Discovery of Tetrahydroisoquinoline-Based CXCR4 Antagonists. ACS Med. Chem. Lett. 2013, 4(11), 1025- 1030. Truax, V.; Zhao, H.; Katzman, B.; Prosser, A.; Alcaraz, A.; Saindane, Manohar T.; Howard, R.; Culver, D.; Arrendale, R.; Gruddanti, P., Taylor, J.E., Natchus, M.; Snyder, J.; Liotta, D.; Wilson, L.
Structure-Activity Relationships and Pharmacophore Model of a Noncompetitive Pyrazoline Containing a Class of GluN2C/GluN2D Selective Antagonists. J. Med. Chem. 2013, 56(16), 6434-6456. Acker,T.; Khatri, A.; Vance, K.; Slabber, C.; Bacsa, J.; Snyder, J.; Traynelis, S.; Liotta, D.
Synthesis and Metabolic Studies of Host-Directed Inhibitors for Antiviral Therapy. ACS Med. Chem. Lett. 2013, 4(8), 762-767. Moore, T.; Sana, K.; Yan, D.; Krumm, S.; Thepchatri, P.; Snyder, J.; Marengo, J.; Arrendale, R.; Prussia, A.; Natchus, M.; Liotta, D.