Mahmoud Kiaei, Ph.D.

Assistant Professor
Phone: (501) 686-7936
Fax:  (501) 686-5521
Mkiaei@uams.edu

Deputy Chief Editor of Metabolic Brain disease
https://www.springer.com/biomed/neuroscience/journal/11011/PS2?detailsPage=editorialBoard

Editorial Board member of J. Neuroinflamation
https://jneuroinflammation.biomedcentral.com/

Editorial Board member of Basic and Clinical Neuroscience

Education

Ph.D. – University of Otago, New Zealand, 1992
Resident Fellow – Mt. Sinai Medical Center, Neurobiology Dept., 1997 – 2000
Sr. Resident Fellow – Weill Medical College of Cornell University, 2000 – 2005

Research Interests

The main goal of the research in Kiaei lab is to understand the process of neurodegeneration (e.g. in amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s Disease), mimic the disease in the lab and develop an effective therapy for this currently “cureless” disease.

The Kiaei laboratory is equipped with expertise to develop animal models to study motor neuron disease. We utilize our extensive experience on pre-clinical studies for diseases like ALS to unravel the mechanism of neurodegeneration. The Kiaei lab uses these resources to develop drug discovery strategies to fulfill the unmet need of patients. Our studies on the SOD1-based mouse model and other models for ALS that mimic the human disease have generated significantly important insights into the mechanisms underlying the pathogenesis of ALS. A breakthrough in using the SOD1 mouse model, we discovered a powerful neuroprotective cellular signaling system, the Nrf2/ARE pathway, which is a major target controlling a majority of genes (over 200 phase 2 genes) involved in stress, inflammation and mitochondrial dysfunction. We have developed a library of promising compounds for the activation of the Nrf2/ARE pathway and other neuroprotective pathways to block neurodegeneration.

Recently, the Kiaei laboratory developed a novel technology in Compositions and Methods for Modulating Neuronal Degeneration (patent pending) and have created a novel, human profilin1 (hPFN1) mutant mouse model that would enable us to examine molecular mechanism of ALS from a new perspective, i.e. cytoskeletal dysfunction, synaptic dynamics, dendrite and axonal integrity, and maintenance.

This new PFN1 mutant mouse model (Fil et al., 2017, https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/ddw429) is a much needed new tool to study neurodegeneration and learn about the pathways that weren’t possible to explore before. For example, the profilin1 protein’s proper function is critical for actin polymerization and cytoskeletal dynamics in the central nervous system. This new tool is excellent to study actin polymerization with respect to neurodegeneration. This model’s multiple utilities (mechanism, target identification and therapeutic strategy development) will enable us to contribute to the field of neurodegeneration and pre-clinical drug development and to conduct studies on drug validation for ALS. The Kiaei lab is studying PFN1 alongside SOD1 mutant mice to discover and identify novel pathways and targets, with consensus on the mechanism(s) and therapeutic strategies that would have greater potential for therapeutic effectiveness in human ALS patients. The transgenic wild-type and mutant PFN1 (G118V) mice are now available to order from JAX Mice at https://www.jax.org (Stock No:030570, PrP-hPFN1WT C57BL/6N-Tg(Prnp-PFN1)850Kiaei/J, Stock No:030568 PrP-hPFN1G118V C57BL/6N-Tg(Prnp-PFN1*G118V)838Kiaei/J)

Meet Dr. Kiaei’s Research Team

Learn more about Transgenic ALS Mice Research

Recent Research Support

Current Research
R03 NS101334 (PI)  (04/01/07 – 03/30/19)
“Alpha-Tubulin Mutation and Motor Neuron”

UAMS Intramural grants  (PI)  (01/10/10-no end date)
“Department of Neurobiology and Developmental Sciences, Center for Translational Neuroscience”

R21 NS088652-01A1  (PI)  (05/15/15 – 04/30/17)
“Development of a New ALS Mouse Model that Targets Profilin 1 and Actin Filaments”

Completed Research
Research Council Pilot Study Award  (PI)  (01/04/14 – 03/30/15)
“Development of a New ALS Mouse Model that Targets Profilin 1 and Actin Filaments”

COBRE Pilot Study Award  (PI)  (01/05/14 – 03/04/15)
“Development of a New ALS Mouse Model that Targets Profilin 1 and Actin Filaments”

Publications

Fil D, DeLoach A, Yadav S, Alkam D, MacNicol M, Singh A, Compadre CM, Goellner JJ, O’Brien CA, Fahmi T, Basnakian AG, Calingasan NY, Klessner JL, Beal FM, Peters OM, Metterville J, Brown RH Jr, Ling KKY, Rigo F, Ozdinler PH, Kiaei M. Hum Mol Genet. 26(4):686-701, 2017 (PMID: 28040732).

Alkam D, Feldman EZ, Singh A, Kiaei M. Profilin1 biology and its mutation, actin(g) in disease. Cell Mol Life Sci. 2016 [Epub] (PMID: 27669692).

Esmaeili MA, Yadav S, Gupta RK, Waggoner GR, Deloach A, Calingasan NY, Beal MF, Kiaei M. Preferential PPAR-α activation reduces neuroinflammation, and blocks neurodegeneration in vivo. Hum Mol Genet. 25(2):317-27, 2016 (PMID: 26604138).

DeLoach A, Cozart M, Kiaei A, Kiaei M. A retrospective review of the progress in amyotrophic lateral sclerosis drug discovery over the last decade and a look at the latest strategies. Expert Opin Drug Discov.10(10):1099-118, 2015 (PMID: 26307158).

Esmaeili MA, Farimani MM, Kiaei M. Anticancer effect of calycopterin via PI3K/Akt and MAPK signaling pathways, ROS-mediated pathway and mitochondrial dysfunction in hepatoblastoma cancer (HepG2) cells. Mol Cell Biochem. 397(1-2):17-31, 2014 (PMID: 25060910).

Compadre CM, Singh A, Thakkar S, Zheng G, Breen PJ, Ghosh S, Kiaei M, Boerma M, Varughese KI, Hauer-Jensen M. Molecular dynamics guided design of tocoflexol: a new radioprotectant tocotrienol with enhanced bioavailability. Drug Dev Res. 75(1):10-22, 2014 (PMID: 24648045).

Ansari N, Hadi-Alijanvand H, Sabbaghian M, Kiaei M, Khodagholi F. Interaction of 2-APB, dantrolene, and TDMT with IP3R and RyR modulates ER stress-induced programmed cell death I and II in neuron-like PC12 cells: an experimental and computational investigation. J Biomol Struct Dyn. 32(8):1211-30c, 2014 (PMID: 23829337)

Digaleh H, Kiaei M, Khodagholi F. Nrf2 and Nrf1 signaling and ER stress crosstalk: implication for proteasomal degradation and autophagy. Cell Mol Life Sci. 70(24):4681-94, 2013 (PMID: 23800989).

Franco MC, Ye Y, Refakis CA, Feldman JL, Stokes AL, Basso M, Melero Fernández de Mera RM, Sparrow NA, Calingasan NY, Kiaei M, Rhoads TW, Ma TC, Grumet M, Barnes S, Beal MF, Beckman JS, Mehl R, Estévez AG. Nitration of Hsp90 induces cell death. Proc Natl Acad Sci U S A. 110(12):E1102-11, 2013 (PMID: 23487751).

Esmaeili MA, Panahi M, Yadav S, Hennings L, Kiaei M. Premature death of TDP-43 (A315T) transgenic mice due to gastrointestinal complications prior to development of full neurological symptoms of amyotrophic lateral sclerosis. Int J Exp Pathol. 94(1):56-64, 2013 (PMID: 23317354).

Morrison B, Hensley K, Pioro EP, Petri S, Kiaei M. Amyotrophic lateral sclerosis and novel therapeutic strategies. Neurol Res Int. 2012:798028, 2012 (PMID: 23316357).

View Dr. Kiaei’s Publication List