Ismael Al-Ramahi, Ph.D.

Assistant Professor

(832) 824-8122

Email

ismael.alramahi@bcm.edu

Positions

Assistant Professor: Molecular and Human Genetics
Jan and Dan Duncan Neurological Research Institute
Baylor College of Medicine
Houston, TX, US

Addresses

Jan and Dan Duncan Neurological Research Institute (Office): 1250 Moursund St.
Room: Suite-N1025.20
Houston, TX, 77030
United States
Phone: (832) 824-8122

Education

BS from Univerisdad Autonoma: 06/2001 - Madrid, Spain

PhD from Universidad Autonoma: 11/2007 - Madrid, Spain

Postdoctoral Fellowship at Baylor College of Medicine: Houston, United States

Websites

Center for Alzheimer’s and Neurodegenerative Diseases

The Center for Alzheimer’s and Neurodegenerative Diseases (CAND) integrates cross-disciplinary clinical, research, and educational programs to advance precision diagnosis and personalized therapies for Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative conditions.

Jan and Dan Duncan Neurological Research Institute

VIICTR Publications List

Selected Publications

George A Edwards 3rd, Caleb A Wood, Yang He, Quynh Nguyen, Peter J Kim, Ruben Gomez-Gutierrez, Kyung-Won Park, Yong Xu, Cody Zurhellen, Ismael Al-Ramahi, Joanna L Jankowsky. " TMEM106B coding variant is protective and deletion detrimental in a mouse model of tauopathy " Acta Neuropathol.. 2024 Mar 25; 147 (61)
Pubmed PMID: 38526616.
T. Bourquard, K. Lee, Ismael Al-Ramahi (Co-First), M. Pham, D. Shapiro, Y. Lagisetty, S. Soleimani, S. Mota, K. Wilhelm, M. Samieinasab, Y. W. Kim, E. Huh, J. Asmussen, P. Katsonis, J. Botas, O. Lichtarge. " Functional variants identify sex-specific genes and pathways in Alzheimer’s Disease " Nat Commun.. 2023 May 13; 14 (2765)
Pubmed PMID: 37179358.
Al-Ramahi I, Lu B, Di Paola S, Pang K, de Haro M, Peluso I, Gallego-Flores T, Malik NT, Erikson K, Bleiberg BA, Avalos M, Fan G, Rivers LE, Laitman AM, Diaz-García JR, Hild M, Palacino J, Liu Z, Medina DL, Botas J.. " High-Throughput Functional Analysis Distinguishes Pathogenic, Nonpathogenic, and Compensatory Transcriptional Changes in Neurodegeneration. " Cell Syst.. 2018 Jul ;
Pubmed PMID: 29936182.
Young Won Kim, Ismael Al-Ramahi (Co-First), Amanda Koire, Stephen J Wilson, Daniel M Konecki, Samantha Mota, Shirin Soleimani, Juan Botas, Olivier Lichtarge. " Harnessing the paradoxical phenotypes of APOE ɛ2 and APOE ɛ4 to identify genetic modifiers in Alzheimer's disease " Alzheimers Dement.. 2020 Dec 7; 17 (5)
Pubmed PMID: 33576571.
Al-Ramahi I, Giridharan SSP, Chen YC, Patnaik S, Safren N, Hasegawa J, de Haro M, Wagner Gee AK, Titus SA, Jeong H, Clarke J, Krainc D, Zheng W, Irvine RF, Barmada S, Ferrer M, Southall N, Weisman LS, Botas J, Marugan JJ.. " Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein. " Elife. 2017 Dec ;
Pubmed PMID: 29256861.
select Stephens MC, Li J, Mair M, Moore J, Zhu K, Tarkunde A, Amoh B, Perez AM, Bhakare A, Guo F, Shulman JM, Al-Ramahi I, Botas J. " Computational and functional prioritization identifies genes that rescue behavior and reduce tau protein in fly and human cell models of Alzheimer disease. " Am J Hum Genet. 2025 May 1; 112 (5) : 1081-1096.
Pubmed PMID: 40215969.
Spargo TP, Sands CF, Juan IR,..., Hollis B, Cuddapah VA, Zoghbi HY, Shulman JM, Petrovski S, Al-Ramahi I, Tachmazidou I, Dhindsa RS. " Haploinsufficiency of ITSN1 is associated with a substantial increased risk of Parkinson's disease " Cell Rep. 2025 Mar 25; 44 (3)
Pubmed PMID: 40056900.
Moore J, Wu T, Dhindsa J, El Fadel O, Le A, Perez A, Amoh B, Tarkunde A, Zhu KF, Avalos M, Dammer EB, Duong DM, Seyfried NT, Shulman JM, Al-Ramahi I, Botas J. " Longitudinal multi-omics in alpha-synuclein Drosophila model discriminates disease- from age-associated pathologies in Parkinson's disease " NPJ Parkinsons Dis. 2025 Mar 11; 11 (46)
Pubmed PMID: 40069190.
Wu T, Deger JM, Ye H, Guo C, Dhindsa J, Pekarek BT, Al-Ouran R, Liu Z, Al-Ramahi Ismael, Botas J, Shulman JM.. " Tau polarizes an aging transcriptional signature to excitatory neurons and glia. " Elife. 2023 May 23; 12
Pubmed PMID: 37219079.
Yu M, Ye H, De-Paula RB, Mangleburg CG, Wu T, Lee TV, Li Y, Duong D, Phillips B, Cruchaga C, Allen GI, Seyfried NT, Al-Ramahi Ismael, Botas J, Shulman JM.. " Functional screening of lysosomal storage disorder genes identifies modifiers of alpha-synuclein neurotoxicity " PLoS Genet.. 2023 May 18; 19 (5)
Pubmed PMID: 37200393.
R. Benyair, S. S. P. Giridharan, P. Rivero-Ríos, J. Hasegawa, E. Bristow, Eeva-Liisa Eskelinen, M. D. Shmueli, V. Fishbain-Yoskovitz, Y. Merbl, L. M. Sharkey, H. L. Paulson, P. I. Hanson, S. Patnaik, Ismael Al-Ramahi, J. Botas, J. Marugan, L. S. Weisman. " Upregulation of the ESCRT pathway and multivesicular bodies accelerates degradation of proteins associated with neurodegeneration " Autophagy Rep.. 2023 Apr 13; 2(1) (2166722)
Pubmed PMID: 37064812.
Jiyoen Kim, Maria de Haro, Ismael Al-Ramahi, Lorena Laura Garaicoechea, Hyun-Hwan Jeong, Jun Young Sonn, Bakhos Tadros, Zhandong Liu, Juan Botas, Huda Yahya Zoghbi. " Evolutionarily conserved regulators of tau identify targets for new therapies " Neuron. 2023 Mar 15; 111 (6) : 824-838.
Pubmed PMID: 36610398.
Y. Lagisetty, T. Bourquard, Ismael Al-Ramahi, C. G.Mangleburg, S. Mota, S. Soleimani, J. M. Shulman, J. Botas, K. Lee, O. Lichtarge. " Identification of risk genes for Alzheimer's disease by gene embedding " Cell Genom.. 2022 Sep 14; 2(9) (100162)
Pubmed PMID: 36268052.
J. Li, B. K. Amoh, E. McCormick, A. Tarkunde, K. F. Zhu, A. Perez, M. Mair, J. Moore, J. M Shulman, Ismael Al-Ramahi, J. Botas. " Integration of transcriptome-wide association study with neuronal dysfunction assays provides functional genomics evidence for Parkinson's disease genes " Hum Mol Genet .. 2023 Jan 27; 32 (4) : 685–695.
Pubmed PMID: 36173927.
Won-Seok Lee, Ismael Al-Ramahi, Hyun-Hwan Jeong, Youjin Jang, Tao Lin, Carolyn J. Adamski, Laura A. Lavery, Smruti Rath, Ronald Richman, Vitaliy V. Bondar, Elizabeth Alcala, Jean-Pierre Revelli, Harry T. Orr, Zhandong Liu, Juan Botas, and Huda Y. Zoghbi. " Cross-species genetic screens identify transglutaminase 5 as a regulator of polyglutamine-expanded ataxin-1 " J Clin Invest .. 2022 May 2; 132 (9)
Pubmed PMID: 35499073.
Todd M Greco, Christopher Secker, Eduardo Silva Ramos, Joel D Federspiel, Jeh-Ping Liu, Alma M Perez, Ismael Al-Ramahi, Jeffrey P Cantle, Jeffrey B Carroll, Juan Botas, Scott O Zeitlin, Erich E Wanker, Ileana M Cristea. " Dynamics of huntingtin protein interactions in the striatum identifies candidate modifiers of Huntington disease " Cell Syst.. 2022 Apr 20; 13 (4) : 304-320.
Pubmed PMID: 35148841.
Xiaodan Zhang, Xue Wen, Ismael Al-Ramahi, Juan Botas, Boxun Lu, Yuhua Fu. " Inhibition of HIPK3 by AST487 Ameliorates Mutant HTT-Induced Neurotoxicity and Apoptosis via Enhanced Autophagy " Neurosci Bull.. 2022 Jan ; 38 (1) : 99-103.
Pubmed PMID: 34741261.
Onur TS, Laitman A, Zhao H, Keyho R, Kim H, Wang J, Mair M, Wang H, Li L, Perez A, de Haro M, Wan YW, Allen G, Lu B, Al-Ramahi I, Liu Z, Botas J.. " Downregulation of glial genes involved in synaptic function mitigates Huntington's disease pathogenesis " Elife.. 2021 Apr 19;
Pubmed PMID: 33871358.
Suart CE, Perez AM, Al-Ramahi I, Maiuri T, Botas J, Truant R.. " Spinocerebellar Ataxia Type 1 protein Ataxin-1 is signaled to DNA damage by ataxia-telangiectasia mutated kinase " Hum Mol Genet.. 2021 May 17; 30 (8) : 706-715.
Pubmed PMID: 33772540.
Lee WS, Lavery L, Rousseaux MWC, Rutledge EB, Jang Y, Wan YW, Wu SR, Kim W, Al-Ramahi I, Rath S, Adamski CJ, Bondar VV, Tewari A, Soleimani S, Mota S, Yalamanchili HK, Orr HT, Liu Z, Botas J, Zoghbi HY.. " Dual targeting of brain region-specific kinases potentiates neurological rescue in Spinocerebellar ataxia type 1 " EMBO J .. 2021 Apr 1; 40 (7)
Pubmed PMID: 33709453.
Huichalaf CH, Al-Ramahi I, Park KW, Grunke SD, Lu N, de Haro M, El-Zein K, Gallego-Flores T, Perez AM, Jung SY, Botas J, Zoghbi HY, Jankowsky JL.. " Cross-species genetic screens to identify kinase targets for APP reduction in Alzheimer's disease " Hum Mol Genet .. 2019 Jun 15; 28 (12) : 2014-2029.
Pubmed PMID: 30753434.
Maxime W.C. Rousseaux, Gabriel E. Vázquez-Vélez, Ismael Al-Ramahi, Hyun-Hwan Jeong, Aleksandar Bajic, Jean-Pierre Revelli, Hui Ye, Emily T. Phan, Jennifer M. Deger, Alma M. Perez, Ji-Yoen Kim, Laura A. Lavery, Qikia Xu, Mamie Z. Li, et. al.. " A druggable genome screen identifies modifiers of α-synuclein levels via a tiered cross-species validation approach " Journal of Neuroscience. 2018 Sep ;
Lasagna-Reeves CA, de Haro M, Hao S, Park J, Rousseaux MW, Al-Ramahi I, Jafar-Nejad P, Vilanova-Velez L, See L, De Maio A, Nitschke L, Wu Z, Troncoso JC, Westbrook TF, Tang J, Botas J, Zoghbi HY.. " Reduction of Nuak1 Decreases Tau and Reverses Phenotypes in a Tauopathy Mouse Model. " Neuron. 2016 Oct ;
Pubmed PMID: 27720485.
Rousseaux MW, de Haro M, Lasagna-Reeves CA, De Maio A, Park J, Jafar-Nejad P, Al-Ramahi I, Sharma A, See L, Lu N, Vilanova-Velez L, Klisch TJ, Westbrook TF, Troncoso JC, Botas J, Zoghbi HY.. " TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau. " Elife. 2016 Oct ;
Pubmed PMID: 27779468.
Soriano S, Calap-Quintana P, Llorens JV, Al-Ramahi I, Gutiérrez L, Martínez-Sebastián MJ, Botas J, Moltó MD.. " Metal Homeostasis Regulators Suppress FRDA Phenotypes in a Drosophila Model of the Disease. " PLoS One.. 2016 Jul ;
Pubmed PMID: 27433942.
Langfelder P, Cantle JP, Chatzopoulou D, Wang N, Gao F, Al-Ramahi I, Lu XH, Ramos EM, El-Zein K, Zhao Y, Deverasetty S, Tebbe A, Schaab C, Lavery DJ, Howland D, Kwak S, Botas J, Aaronson JS, Rosinski J, Coppola G, Horvath S, Yang XW.. " Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice. " Nat Neurosci.. 2016 Apr ;
Pubmed PMID: 26900923.
El-Daher MT, Hangen E, Bruyère J, Poizat G, Al-Ramahi I, Pardo R, Bourg N, Souquere S, Mayet C, Pierron G, Lévêque-Fort S, Botas J, Humbert S, Saudou F.. " Huntingtin proteolysis releases non-polyQ fragments that cause toxicity through dynamin 1 dysregulation. " Embo J. 2015 Jul ;
Pubmed PMID: 26165689.
Calap-Quintana P, Soriano S, Llorens JV, Al-Ramahi I, Botas J, Moltó MD, Martínez-Sebastián MJ.. " TORC1 Inhibition by Rapamycin Promotes Antioxidant Defences in a Drosophila Model of Friedreich's Ataxia. " PLoS One.. 2015 Jul ;
Pubmed PMID: 26158631.
Yao Y, Cui X, Al-Ramahi I, Sun X, Li B, Hou J, Difiglia M, Palacino J, Wu ZY, Ma L, Botas J, Lu B.. " A striatal-enriched intronic GPCR modulates huntingtin levels and toxicity. " Elife.. 2015 Mar ;
Pubmed PMID: 25738228.
Lu XH, Mattis VB, Wang N, Al-Ramahi I, van den Berg N, Fratantoni SA, Waldvogel H, Greiner E, Osmand A, Elzein K, Xiao J, Dijkstra S, de Pril R, Vinters HV, Faull R, Signer E, Kwak S, Marugan JJ, Botas J, Fischer DF, Svendsen CN, Munoz-Sanjuan I, Yang XW.. " Targeting ATM ameliorates mutant Huntingtin toxicity in cell and animal models of Huntington's disease. " Sci Transl Med.. 2014 Dec ;
Pubmed PMID: 25540325.
Park J, Al-Ramahi I, Tan Q, Mollema N, Diaz-Garcia JR, Gallego-Flores T, Lu HC, Lagalwar S, Duvick L, Kang H, Lee Y, Jafar-Nejad P, Sayegh LS, Richman R, Liu X, Gao Y, Shaw CA, Arthur JS, Orr HT, Westbrook TF, Botas J, Zoghbi HY.. " RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. " Nature.. 2013 Jun ;
Pubmed PMID: 23719381.
de Haro M, Al-Ramahi I, Jones KR, Holth JK, Timchenko LT, Botas J.. " Smaug/SAMD4A restores translational activity of CUGBP1 and suppresses CUG-induced myopathy. " PLoS Genet.. 2013 Apr ;
Pubmed PMID: 23637619.
Lu B, Al-Ramahi I, Valencia A, Wang Q, Berenshteyn F, Yang H, Gallego-Flores T, Ichcho S, Lacoste A, Hild M, Difiglia M, Botas J, Palacino J.. " Identification of NUB1 as a suppressor of mutant Huntington toxicity via enhanced protein clearance. " Nat Neurosci.. 2013 May ;
Pubmed PMID: 23525043.
Miller JP, Yates BE, Al-Ramahi I, Berman AE, Sanhueza M, Kim E, de Haro M, DeGiacomo F, Torcassi C, Holcomb J, Gafni J, Mooney SD, Botas J, Ellerby LM, Hughes RE.. " A genome-scale RNA-interference screen identifies RRAS signaling as a pathologic feature of Huntington's disease. " PLoS Genet.. 2012 Nov ;
Pubmed PMID: 23209424.
Shirasaki DI, Greiner ER, Al-Ramahi I, Gray M, Boontheung P, Geschwind DH, Botas J, Coppola G, Horvath S, Loo JA, Yang XW.. " Network organization of the huntingtin proteomic interactome in mammalian brain. " Neuron.. 2012 Jul ;
Pubmed PMID: 22794259.
Zhang N, Li B, Al-Ramahi I, Cong X, Held JM, Kim E, Botas J, Gibson BW, Ellerby LM.. " Inhibition of lipid signaling enzyme diacylglycerol kinase epsilon attenuates mutant huntingtin toxicity. " J Biol Chem.. 2012 Jun ;
Pubmed PMID: 22511757.
Miller JP, Holcomb J, Al-Ramahi I, de Haro M, Gafni J, Zhang N, Kim E, Sanhueza M, Torcassi C, Kwak S, Botas J, Hughes RE, Ellerby LM.. " Matrix metalloproteinases are modifiers of huntingtin proteolysis and toxicity in Huntington's disease. " Neuron.. 2010 Jul ;
Pubmed PMID: 20670829.
de Haro M, Al-Ramahi I, Benito-Sipos J, López-Arias B, Dorado B, Veenstra JA, Herrero P.. " Detailed analysis of leucokinin-expressing neurons and their candidate functions in the Drosophila nervous system. " Cell Tissue Res.. 2010 Feb ;
Pubmed PMID: 19941006.
Al-Ramahi I, Pérez AM, Lim J, Zhang M, Sorensen R, de Haro M, Branco J, Pulst SM, Zoghbi HY, Botas J.. " dAtaxin-2 mediates expanded Ataxin-1-induced neurodegeneration in a Drosophila model of SCA1. " PLoS Genet.. 2007 Dec ;
Pubmed PMID: 18166084.
Branco J, Al-Ramahi I, Ukani L, Pérez AM, Fernandez-Funez P, Rincón-Limas D, Botas J.. " Comparative analysis of genetic modifiers in Drosophila points to common and distinct mechanisms of pathogenesis among polyglutamine diseases. " Hum Mol Genet.. 2008 Feb ;
Pubmed PMID: 17984172.
Al-Ramahi I, Lam YC, Chen HK, de Gouyon B, Zhang M, Pérez AM, Branco J, de Haro M, Patterson C, Zoghbi HY, Botas J.. " CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation. " J Biol Chem.. 2006 Sep ;
Pubmed PMID: 16831871.
de Haro M, Al-Ramahi I, De Gouyon B, Ukani L, Rosa A, Faustino NA, Ashizawa T, Cooper TA, Botas J.. " MBNL1 and CUGBP1 modify expanded CUG-induced toxicity in a Drosophila model of myotonic dystrophy type 1. " Hum Mol Genet.. 2006 Jul ;
Pubmed PMID: 16723374.

Funding

Decoding the impact of sex differences on Alzheimer's disease risk #R01AG074009: $6,009,110.00 (06/30/2021 - 07/01/2026); Grant funding from NIH-NIA; Alzheimer's disease affects approximately twice as many females compared to males. The reasons for this difference are largely unexplored. We combine computational approaches applied to whole exome/genome sequencing of patients and controls with in vivo (Drosophila, cells, mice) approaches to identify genes that carry differential risk of causing Alzheimer's disease in females and in males.

2016-2019 Behavioral and cell-based complementary screens to identify druggable targets modulating tau protein levels #5R21NS096395: Grant funding from NIH-NIA