UAMS.EDU

Mahmoud Kiaei, Ph.D.

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

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

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

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

This new PFN1 mutant mouse model (Manuscript is provisionally accepted by Human Molecular Genetics) is our new tool to study cytoskeletal dysfunction utilizing profilin1 as key enzyme in the polymerization of actin. 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 conduct studies on drug validation for ALS. We plan to use PFN1 in conjunction with SOD1 mutant mice to discover and identify pathways and targets with consensus on the mechanism(s) and therapeutic strategies which would have greater potential for therapeutic effectiveness in human ALS patients.

The PFN1 mouse model will be used to learn about cytoskeletal defects that this model will be highly advantages. Therefore, we are highly interested to train students and postdocs in these area. We are also very keen to collaborate with laboratories that has expertise in cytoskeletal dysfunction and axonal dynamics.

Meet Dr. Kiaei’s Research Team

Learn more about Transgenic ALS Mice Research

Recent Research Support

Current Research
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

Alkam D, Feldman EZ, Singh A, Kiaei M. Profilin1 biology and its mutation, actin(g) in disease. Cell Mol Life Sci. 2016 Sep 26. [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