Tyrone DeSpenza Jr, MD, PhD

Headshot of Tyronne DeSpenza
PGY-1

Education 

Yale School of Medicine, MD, 2024
Yale School of Medicine, PhD, Neuroscience, 2023
Dartmouth College, AB, Neuroscience with Honors, 2013

Honors and Awards

  • The MD-PhD Award, Yale Medical Scientist Training Program, 2024
  • Hydrocephalus Association Travel Award, The Hydrocephalus Association, 2022
  • Best Neuroscience Oral Presentation, National MD/PhD Student Conference, 2022
  • Ruth L. Kirschstein Predoctoral Individual NRSA F31 Award, NINDS, 2020
  • Neuroscience Center at Dartmouth Award for Excellence in Neuroscience Thesis Presentation, 2013
  • Neuroscience Center at Dartmouth Honors Thesis Prize, 2013
  • Sigma Xi Reed Competition Award, Dartmouth College, 2013

Research Interests

Neurodevelopment, genetics, neuro-oncology

Hobbies

Golf, running, jazz, alto saxophone

Publications

DeSpenza T Jr, Singh A, Allington G, Zhao S, Lee J, Kizlitug E, Prina ML, Desmet N, Dang HQ, Fields J, Nelson-Williams C, Zhang J, Mekbib KY, Dennis E, Mehta NH, Duy PQ, Shimelis H, Walsh LK, Marlier A, Deniz E, Lake EMR, Constable RT, Hoffman EJ, Lifton RP, Gulledge A, Fiering S, Moreno-De-Luca A, Haider S, Alper SL, Jin SC, Kahle KT, Luikart BW. Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics. Proc Natl Acad Sci U S A. 2024 Jul 2;121(27):e2314702121. doi: 10.1073/pnas.2314702121. Epub 2024 Jun 25. PubMed PMID: 38916997.

 
Singh AK, Allington G, Viviano S, McGee S, Kiziltug E, Ma S, Zhao S, Mekbib KY, Shohfi JP, Duy PQ, DeSpenza T Jr, Furey CG, Reeves BC, Smith H, Sousa AMM, Cherskov A, Allocco A, Nelson-Williams C, Haider S, Rizvi SRA, Alper SL, Sestan N, Shimelis H, Walsh LK, Lifton RP, Moreno-De-Luca A, Jin SC, Kruszka P, Deniz E, Kahle KT. A novel SMARCC1 BAFopathy implicates neural progenitor epigenetic dysregulation in human hydrocephalus. Brain. 2024 Apr 4;147(4):1553-1570. doi: 10.1093/brain/awad405. PubMed PMID: 38128548; PubMed Central PMCID: PMC10994532.
 
Mekbib KY, Muñoz W, Allington G, McGee S, Mehta NH, Shofi JP, Fortes C, Le HT, Nelson-Williams C, Nanda P, Dennis E, Kundishora AJ, Khanna A, Smith H, Ocken J, Greenberg ABW, Wu R, Moreno-De-Luca A, DeSpenza T Jr, Zhao S, Marlier A, Jin SC, Alper SL, Butler WE, Kahle KT. Human genetics and molecular genomics of Chiari malformation type 1. Trends Mol Med. 2023 Dec;29(12):1059-1075. doi: 10.1016/j.molmed.2023.08.013. Epub 2023 Oct 4. Review. PubMed PMID: 37802664.
 
Zhao S, Mekbib KY, van der Ent MA, Allington G, Prendergast A, Chau JE, Smith H, Shohfi J, Ocken J, Duran D, Furey CG, Hao LT, Duy PQ, Reeves BC, Zhang J, Nelson-Williams C, Chen D, Li B, Nottoli T, Bai S, Rolle M, Zeng X, Dong W, Fu PY, Wang YC, Mane S, Piwowarczyk P, Fehnel KP, See AP, Iskandar BJ, Aagaard-Kienitz B, Moyer QJ, Dennis E, Kiziltug E, Kundishora AJ, DeSpenza T Jr, Greenberg ABW, Kidanemariam SM, Hale AT, Johnston JM, Jackson EM, Storm PB, Lang SS, Butler WE, Carter BS, Chapman P, Stapleton CJ, Patel AB, Rodesch G, Smajda S, Berenstein A, Barak T, Erson-Omay EZ, Zhao H, Moreno-De-Luca A, Proctor MR, Smith ER, Orbach DB, Alper SL, Nicoli S, Boggon TJ, Lifton RP, Gunel M, King PD, Jin SC, Kahle KT. Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations. Nat Commun. 2023 Nov 17;14(1):7452. doi: 10.1038/s41467-023-43062-z. PubMed PMID: 37978175; PubMed Central PMCID: PMC10656524.
 
Robert SM, Reeves BC, Kiziltug E, Duy PQ, Karimy JK, Mansuri MS, Marlier A, Allington G, Greenberg ABW, DeSpenza T Jr, Singh AK, Zeng X, Mekbib KY, Kundishora AJ, Nelson-Williams C, Hao LT, Zhang J, Lam TT, Wilson R, Butler WE, Diluna ML, Feinberg P, Schafer DP, Movahedi K, Tannenbaum A, Koundal S, Chen X, Benveniste H, Limbrick DD Jr, Schiff SJ, Carter BS, Gunel M, Simard JM, Lifton RP, Alper SL, Delpire E, Kahle KT. The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus. Cell. 2023 Feb 16;186(4):764-785.e21. doi: 10.1016/j.cell.2023.01.017. PubMed PMID: 36803604; PubMed Central PMCID: PMC10069664.
 
Duy PQ, Weise SC, Marini C, Li XJ, Liang D, Dahl PJ, Ma S, Spajic A, Dong W, Juusola J, Kiziltug E, Kundishora AJ, Koundal S, Pedram MZ, Torres-Fernández LA, Händler K, De Domenico E, Becker M, Ulas T, Juranek SA, Cuevas E, Hao LT, Jux B, Sousa AMM, Liu F, Kim SK, Li M, Yang Y, Takeo Y, Duque A, Nelson-Williams C, Ha Y, Selvaganesan K, Robert SM, Singh AK, Allington G, Furey CG, Timberlake AT, Reeves BC, Smith H, Dunbar A, DeSpenza T Jr, Goto J, Marlier A, Moreno-De-Luca A, Yu X, Butler WE, Carter BS, Lake EMR, Constable RT, Rakic P, Lin H, Deniz E, Benveniste H, Malvankar NS, Estrada-Veras JI, Walsh CA, Alper SL, Schultze JL, Paeschke K, Doetzlhofer A, Wulczyn FG, Jin SC, Lifton RP, Sestan N, Kolanus W, Kahle KT. Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus. Nat Neurosci. 2022 Apr;25(4):458-473. doi: 10.1038/s41593-022-01043-3. Epub 2022 Apr 4. PubMed PMID: 35379995; PubMed Central PMCID: PMC9664907.
 
DeSpenza T Jr, Carlson M, Panchagnula S, Robert S, Duy PQ, Mermin-Bunnell N, Reeves BC, Kundishora A, Elsamadicy AA, Smith H, Ocken J, Alper SL, Jin SC, Hoffman EJ, Kahle KT. PTEN mutations in autism spectrum disorder and congenital hydrocephalus: developmental pleiotropy and therapeutic targets. Trends Neurosci. 2021 Dec;44(12):961-976. doi: 10.1016/j.tins.2021.08.007. Epub 2021 Oct 5. Review. PubMed PMID: 34625286; PubMed Central PMCID: PMC8692171.
 
Robert SM, Reeves BC, Marlier A, Duy PQ, DeSpenza T, Kundishora A, Kiziltug E, Singh A, Allington G, Alper SL, Kahle KT. Inflammatory hydrocephalus. Childs Nerv Syst. 2021 Nov;37(11):3341-3353. doi: 10.1007/s00381-021-05255-z. Epub 2021 Jun 23. PubMed PMID: 34164718.
 
Jin SC, Dong W, Kundishora AJ, Panchagnula S, Moreno-De-Luca A, Furey CG, Allocco AA, Walker RL, Nelson-Williams C, Smith H, Dunbar A, Conine S, Lu Q, Zeng X, Sierant MC, Knight JR, Sullivan W, Duy PQ, DeSpenza T, Reeves BC, Karimy JK, Marlier A, Castaldi C, Tikhonova IR, Li B, Peña HP, Broach JR, Kabachelor EM, Ssenyonga P, Hehnly C, Ge L, Keren B, Timberlake AT, Goto J, Mangano FT, Johnston JM, Butler WE, Warf BC, Smith ER, Schiff SJ, Limbrick DD Jr, Heuer G, Jackson EM, Iskandar BJ, Mane S, Haider S, Guclu B, Bayri Y, Sahin Y, Duncan CC, Apuzzo MLJ, DiLuna ML, Hoffman EJ, Sestan N, Ment LR, Alper SL, Bilguvar K, Geschwind DH, Günel M, Lifton RP, Kahle KT. Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus. Nat Med. 2020 Nov;26(11):1754-1765. doi: 10.1038/s41591-020-1090-2. Epub 2020 Oct 19. PubMed PMID: 33077954; PubMed Central PMCID: PMC7871900.
 
Allocco AA, Jin SC, Duy PQ, Furey CG, Zeng X, Dong W, Nelson-Williams C, Karimy JK, DeSpenza T, Hao LT, Reeves B, Haider S, Gunel M, Lifton RP, Kahle KT. Recessive Inheritance of Congenital Hydrocephalus With Other Structural Brain Abnormalities Caused by Compound Heterozygous Mutations in ATP1A3. Front Cell Neurosci. 2019;13:425. doi: 10.3389/fncel.2019.00425. eCollection 2019. PubMed PMID: 31616254; PubMed Central PMCID: PMC6775207.
 
Fricano-Kugler CJ, Getz SA, Williams MR, Zurawel AA, DeSpenza T Jr, Frazel PW, Li M, O'Malley AJ, Moen EL, Luikart BW. Nuclear Excluded Autism-Associated Phosphatase and Tensin Homolog Mutations Dysregulate Neuronal Growth. Biol Psychiatry. 2018 Aug 15;84(4):265-277. doi: 10.1016/j.biopsych.2017.11.025. Epub 2017 Dec 2. PubMed PMID: 29373119; PubMed Central PMCID: PMC5984669.
 
Furey CG, Choi J, Jin SC, Zeng X, Timberlake AT, Nelson-Williams C, Mansuri MS, Lu Q, Duran D, Panchagnula S, Allocco A, Karimy JK, Khanna A, Gaillard JR, DeSpenza T, Antwi P, Loring E, Butler WE, Smith ER, Warf BC, Strahle JM, Limbrick DD, Storm PB, Heuer G, Jackson EM, Iskandar BJ, Johnston JM, Tikhonova I, Castaldi C, López-Giráldez F, Bjornson RD, Knight JR, Bilguvar K, Mane S, Alper SL, Haider S, Guclu B, Bayri Y, Sahin Y, Apuzzo MLJ, Duncan CC, DiLuna ML, Günel M, Lifton RP, Kahle KT. De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus. Neuron. 2018 Jul 25;99(2):302-314.e4. doi: 10.1016/j.neuron.2018.06.019. Epub 2018 Jul 5. PubMed PMID: 29983323; PubMed Central PMCID: PMC7839075.
 
Duran D, Jin SC, DeSpenza T Jr, Nelson-Williams C, Cogal AG, Abrash EW, Harris PC, Lieske JC, Shimshak SJ, Mane S, Bilguvar K, DiLuna ML, Günel M, Lifton RP, Kahle KT. Digenic mutations of human OCRL paralogs in Dent's disease type 2 associated with Chiari I malformation. Hum Genome Var. 2016;3:16042. doi: 10.1038/hgv.2016.42. eCollection 2016. PubMed PMID: 28018608; PubMed Central PMCID: PMC5143364.
 
Getz SA, DeSpenza T Jr, Li M, Luikart BW. Rapamycin prevents, but does not reverse, aberrant migration in Pten knockout neurons. Neurobiol Dis. 2016 Sep;93:12-20. doi: 10.1016/j.nbd.2016.03.010. Epub 2016 Mar 15. PubMed PMID: 26992888; PubMed Central PMCID: PMC5409093.
 
Williams MR, DeSpenza T Jr, Li M, Gulledge AT, Luikart BW. Hyperactivity of newborn Pten knock-out neurons results from increased excitatory synaptic drive. J Neurosci. 2015 Jan 21;35(3):943-59. doi: 10.1523/JNEUROSCI.3144-14.2015. PubMed PMID: 25609613; PubMed Central PMCID: PMC4300333.
 
Fricano CJ, Despenza T Jr, Frazel PW, Li M, O'Malley AJ, Westbrook GL, Luikart BW. Fatty acids increase neuronal hypertrophy of Pten knockdown neurons. Front Mol Neurosci. 2014;7:30. doi: 10.3389/fnmol.2014.00030. eCollection 2014. PubMed PMID: 24795563; PubMed Central PMCID: PMC4006057.