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THE MAY KHANNA LABORATORY

Developing small molecule therapeutics for neurodegenerative disease

RESEARCH HIGHLIGHTS

We combine biochemical and biophysical techniques to target key protein-protein and protein-RNA interactions in neurodegenerative disease.

 

PROTEIN-PROTEIN INTERACTIONS IN THE NECROSOME

Chronic inflammation initiates necroptosis, a poorly understood pathway of programmed cell death.  This pathway is mediated by RIPK1 phosphorylation of RIPK3 followed by RIPK3 phosphorylation of MLKL.  We are developing compounds to disrupt the interactions between these proteins without interfering with their normal, vital cell functions.

PROTEIN-PROTEIN AND RNA-PROTEIN INTERACTIONS IN THE RNA EXOSOME

We recently developed a new zebrafish model of the rare neurodegenerative disease pontocerebellar hypoplasia type 1B (PCH1B).  Our rationally designed small-molecule binds to the cap protein EXOSC3, interfering with RNA binding and recapitulating key features of this disease.  This model system provides a platform to screen for new therapeutic approaches for neurodegenerative diseases.

RNA-PROTEIN INTERACTIONS IN ALS

A hallmark of amyotrophic lateral sclerosis (ALS) is the presence of protein-RNA inclusions containing the RNA-binding protein TDP-43.  We are developing small molecules to treat ALS by targeting TDP-43.  In one approach, we aim to disrupt aberrant polymerization driven by self-association of the N-terminal domain.  In another, we aim to disrupt association of the RRM domains with aberrant RNA.

PROTEIN-PROTEIN INTERACTIONS IN AMP-AD TARGETS

Alzheimer's disease is the most common cause of dementia and has no cure.  The Accelerating Medicines Partnership-Alzheimer’s Disease (AMP-AD) project aims to shorten the time between drug discovery and preclinical validation.  We are focused on targeting the interaction between CD44 and three FERM domain proteins in the target list: EPB41L3, Moesin and FERMT2.

THE LATEST LAB NEWS

 

RECENT PUBLICATIONS

 

Karson J Kump,Lei Miao, Ahmed SA Mady, Nurul H Ansari, Uttar K Shrestha, Yuting Yang, Mohan Pal, Chenzhong Liao, Andrej Perdih, Fardokht A Abulwerdi, Krishnapriya Chinnaswamy, Jennifer L Meagher, Jacob M Carlson, May Khanna, Jeanne A Stuckey, Zaneta Nikolovska-Coleska

Journal of Medicinal Chemistry (2020)

doi: 10.1021/acs.jmedchem.9b01442

Discovery and Characterization of 2,5-Substituted Benzoic Acid Dual Inhibitors of the Anti-Apoptotic Mcl-1 and Bfl-1 Proteins

Liberty François-Moutal,  Samantha Perez-Miller, David D. Scott, Victor Miranda, Niloufar Mollasalehi, and May Khanna

Front. Mol. Neurosci. (2019)

doi: 10.3389/fnmol.2019.00301

Structural Insights Into TDP-43 and Effects of Post-translational Modifications

Liberty François-Moutal, David D. Scott, Razaz Felemban, Victor Miranda, Melissa Sayegh, Samantha Perez-Miller, Rajesh Khanna, Vijay Gokhale, Daniela C. Zarnescu and May Khanna

ACS Chem Biol. (2019) 14(9):2006-2013.

doi: 10.1021/acschembio.9b00481

A small molecule targeting TDP-43’s RNA recognition motifs reduces locomotor defects in a Drosophila model of ALS

David D. Scott, Liberty François-Moutal, Vlad K. Kumirov and May Khanna

Biomolecular NMR Assignments. (2019) 13(1):163-167.

doi: 10.1007/s12104-018-09870-x

1H, 15N and 13C backbone assignment of apo TDP-43 RNA recognition motifs

François-Moutal L, Jahanbakhsh S, Nelson A, Ray D, Scott DD, Hennefarth MR, Moutal A, Perez-Miller S, Al-Shamari A, Coursodon P, Meechoovet B, Reiman R, Lyons E, Beilstein M, Morris QD, Van Keuren-Jensen K, Hughes TR, Khanna R, Koehler C, Jen Joanna, Gokhale V, Khanna M.

ACS Chem Biol. (2018) 13(10):3000-3010.

doi: 10.1021/acschembio.8b00745

A Chemical Biology Approach to Model Pontocerebellar Hypoplasia Type 1B (PCH1B).  ACS Chemical Biology

PEOPLE

 

Principal Investigator

MAY KHANNA, PHD

May has over 20 years of experience using multiple biophysical tools including Surface Plasmon Resonance (SPR), Nuclear Magnetic Resonance (NMR) and X-ray Crystallography to define protein-protein, protein-RNA, and and protein-small molecule interactions.  Increasing our understanding of these interactions contributes to the development of novel therapeutics for neurodegenerative disease.​

Post-Doctoral Fellows

LIBERTY FRANÇOIS-MOUTAL, PHD

JONATHAN SANCHEZ, PHD

JUDITH TELLO VEGA, PHD

Lab Technician

JAKE CARLSON

Research Scientist

SAMANTHA PEREZ-MILLER, PHD

Graduate Students

NILOUFAR MOLLASALEHI

DAVID SCOTT

Undergraduate Researchers

VICTOR MIRANDA
AHN LE ANDY

HALEY WILLIAMS

MICHAEL SANDINO

CONTACT US

University of Arizona
Department of Pharmacology

Center for Innovation in Brain Science
Tucson, AZ

USA