About
Myriam Heiman received a B.A. in molecular biology from Princeton University, and a Ph.D. in biology from the Johns Hopkins University. She received her post-doctoral training at the Rockefeller University, working with Dr. Paul Greengard and Dr. Nathaniel Heintz. In 2011 she started her research group at MIT and the Picower Institute. Myriam can be reached at mheiman@mit.edu.
Research
The most common neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases, all display distinct clinical presentations. The basis of these distinct clinical presentations is the enhanced vulnerability of specific neuronal cell types to death or dysfunction in each disease, despite widespread expression of disease-associated genes. The goal of my research group is to elucidate the basis of this enhanced vulnerability in neurodegenerative disease, and we view it as a window for discovering valuable insights into the cell biology of disease-relevant neuronal cell types, while also identifying new therapeutic targets. Our work uses innovative approaches to address these long-standing questions of enhanced vulnerability, including translating ribosome affinity purification (TRAP) and in vivo genome-wide screening in the CNS. Additionally, in recent years my group has used single cell sequencing approaches for the study of the CNS, inducing our recent single cell studies of the human cerebrovasculature, Huntington’s disease, and ALD/FTLD.
Teaching
9.S913, Neurobiology of Disease
Publications
Ament, S., Campbell, R., Lobo, M.K., Receveur, J., Agrawal, K., Borjabad, A., Chang, L., Clarke, D., Cleary, J., Byrareddy, S., Emani, P., Gabuzda, D., Gaulton, K., Giglio, M., Giorgi, F., Gok, B., Guda, C., Hadas, E., Herb, B.R., Hu, W., Huttner, A., Ishmam, M., Jacobs, M., Kelschenbach, J., Kim, D.-W., Lee, C., Liu, X., Liu, S., Madras, B., Mahurkar, A., Mash, D., Mukamel, E., Niu, M., O'Connor, R., Pagan, C., Pang, A., Pillai, P., Repunte-Canonigo, V., Ruzicka, W.R., Stanley, J., Tickle, T., Tsai, S.-Y., Wang, A., Wills, L., Wilson, A., Wright, S., Xu, S., Yang, J., Zand, M., Zhang, L., Zhang, J., Akbarian, S., Buch, S., Cheng, C., Corley, M., Fox, H., Gerstein, M., Gummuluru, S., Heiman, M., Ho, Y.-C., Kellis, M., Kenny, P., Kluger, Y., Milner, T., Moore, D., Morgello, S., Ndhlovu, L., Rana, T., Sanna, P.P., Satterlee, J., Sestan, N., Spector, S., Spudich, S., Tilgner, H., Volsky, D., White, O., Williams, D., and Zeng, H. (2024) The Single-Cell Opioid Responses in the Context of HIV (SCORCH) Consortium. Mol Psychiatry, In Press.
Garcia-Montojo, M., Fathi, S., Rastegar C, Simula, E.R., Doucet-O'Hare, T., Cheng, Y.H.H., Abrams, R.P.M., Pasternack, N., Malik, N., Bachani, M., Disanza, B., Maric, D., Lee, M.H., Wang, H., Santamaria, U., Li, W., Sampson, K., Lorenzo, J.R., Sanchez, I.E., Mezghrani, A., Li, Y., Sechi, L.A., Pineda, S., Heiman, M., Kellis, M., Steiner, J., and Nath, A. (2024) TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression. Nat Commun., 15(1):4163.
Pineda, S.S., Lee, H., Ulloa-Navas, M.J., Linville, R.M., Garcia, F.J., Galani, K., Engelberg-Cook, E., Castanedes, M.C., Fitzwalter, B.E., Pregent, L.J., Gardashli, M.E., Morales-Gallel, R., Garcia-Verdugo, J.M., DeTure, M., Vera-Garcia, D.V., Hucke, A.T.S., Oskarsson, B.E., Murray, M.E., Dickson, D.W., Heiman, M.,1 Belzil, V.V.1, and Kellis, M.1 (2024) Single-cell dissection of the human motor and prefrontal cortices in ALS and FTLD. (1Co-corresponding authors). Cell, 187(8):1971-1989.e16
Huntington’s Disease: Pathogenic Mechanisms and Implications for Therapeutics
Editors: X. Yang, W., Thompson, L.M., and Heiman, M. 1st Edition - February 7, 2024; Elsevier; ISBN: 9780323956727
Fame, R.M., Kalugin, P.N., Petrova, B., Xu, H., Soden, P.A., Shipley, F.B, Dani, N., Grant, B., Pragana, A., Head, J.P., Gupta, S., Shannon, M.L., Chifamba, F.F., Hawks-Mayer, H., Vernon, A., Gao, F., Zhang, Y., Holtzman, M.J., Heiman, M., Andermann, M.L., Kanarek, N., Lipton, J.O., Lehtinen, M.K. (2023) Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution. Nat Commun., 14(1):3720.
Matsushima, A.1, Pineda, S.S.1, Crittenden, J.R., Lee, H., Galani, K., Mantero, J., Tombaugh, G., Kellis, M.2, Heiman, M.2, and Graybiel, A.M.2 (2023) Transcriptional vulnerabilities of striatal neurons in human and rodent models of Huntington's disease. (1Co-first authors; 2Co-corresponding authors). Nat Commun., 14(1):282.
Guillén-Samander, A., Wu, Y., Pineda, S.S., Garcia, F.J., Eisen, J.N., Leonzino, M., Ugur, B., Kellis, M., Heiman, M., and De Camilli, P. (2022). A partnership between the lipid scramblase XK and the lipid
transfer protein VPS13A at the plasma membrane. Proc. Natl. Acad. Sci. USA, 119(35):e2205425119.
Lee, H., and Heiman, M. (2022). Back-to-BACs in Huntington's disease modeling. Neuron, 110(7):1087-1089.
Garcia, F.J., Sun, N., Lee, H., Godlewski, B., Mathys, H., Galani, K., Zhou, B., Jiang, X., Ng, A.P., Mantero, J., Tsai, L-H., Bennett, D.A., Shahin, M., Kellis, M.1, and Heiman, M.1 (2022). Single-cell dissection of the human brain vasculature. (1Co-corresponding authors). Nature, 603(7903):893-899.
Kwon, J-T., Ryu, C.1, Lee, H.1, Sherffield, A., Fan, J., Cho, D., Bigler, S., Sullivan, H.A., Choe, H.K., Wickersham, I.R., Heiman, M., and Choi, G.B. (2021) An amygdala circuit that suppresses social engagement. (1Co-second authors). Nature, 593(7857):114-118.
Mégret, L., Gris, B., Nair, S.S., Cevost, J., Wertz, M. H., Aaronson, J., Rosinski, J., Vogt, T.F., Wilkinson, H., Heiman, M.1, and Néri, C.1 (2021) Temporal dynamics of cell type-specific homeostatic and pathogenic responses to mutant huntingtin. (1Co-corresponding authors). ELife, 10:e64984.
Xu, H.1, Fame, R.M.1, Sadegh, C., Sutin, J., Naranjo, C., Syau, D., Cui, J., Shipley, F.B., Vernon, A., Gao, F., Zhang, Y., Holtzman, M., Heiman, M., Warf, B.C., Lin, P.-Y., and Lehtinen, M.K. (2021) Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development. (1Co-first authors). Nat. Commun., 12(1):447.
Lee, H.1, Fenster, R.J.1, Pineda, S.S.P., Gibbs, W.S., Mohammadi, S., Davila-Velderrain, J., Garcia, F.G., Therrien, M., Novis, H.S., Gao, F., Wilkinson, H., Vogt, T., Kellis, M, LaVoie, M.J., and Heiman M. (2020) Cell Type-Specific Transcriptomics Reveals that Mutant Huntingtin Leads to Mitochondrial RNA Release and Neuronal Innate Immune Activation. (1Co-first authors). Neuron, 107(5), 891-908.
Roussarie, J-P., Yao, V., Rodriguez-Rodriguez, P., Oughtred, R., Rust, J., Plautz, Z., Kasturia, S., Albornoz, C., Wang, W., Schmidt, E.F., Dannenfelser, R., Tadych, A., Brichta, L., Barnea-Cramer, A., Heintz, N., Hof, P.R., Heiman, M., Dolinski, K., Flajolet, M., Troyanskaya, O.G., and Greengard P. (2020) Selective Neuronal Vulnerability in Alzheimer’s Disease: A Network-Based Analysis. Neuron, 107(5), 821-835.
Wertz, M. H., Pineda, S. S., Lee H., Kulicke, R., Kellis, M., and Heiman, M. (2020) Interleukin-6 Deficiency Exacerbates Huntington's Disease Model Phenotypes. Mol. Neurodegener., 15(1):29.
Wertz, M.H., Mitchem, M.R., Pineda, S.S., Hachigian, L.J., Lee, H., Lau, V., Powers, A., Kulicke, R., Lee, H., Madan, G.K., Colic, M., Therrien, M., Vernon, A., Beja-Glasser, V.F., Hegde, M., Gao, F., Kellis, M., Hart, T., Doench, J.G., and Heiman, M. (2020) Genome-wide In Vivo CNS Screening Identifies Genes that Modify CNS Neuronal Survival and mHTT Toxicity. Neuron, 106(1):76-89.
Awards + Honors
Dr. Heiman's work has been recognized by several awards, including a EURKEA award and an R35 outstanding investigator award from the NIH.