Gary D. Smith, PhD

Professor, Molecular & Integrative Physiology
Professor, OB-Gyn
Professor, Urology
Director, MStem Cell Laboratories
Director of Reproductive Sciences Program

4421 Med Sci I 1301 E. Catherine St.
Ann Arbor, MI  48109-0617


Areas of Interest

I.  Regulation of oocyte meiosis and chromatic remodeling with a translational focus of understanding external/endocrine factors, intra-ovarian/oocyte mechanisms of action (kinases and phosphatases), and intra-oocyte substrates that influence meiotic nondisjunction, infertility, normal/abnormal epigenetics/imprinting, and congenital birth defects.  These studies are very basic in nature, but address very real biological problems that contribute to infertility and congenital birth defects.

II.  Basic and applied studies of oocyte cryopreservation.   These studies spanned: i) animal models to assess safety and efficacy of vitrification; ii) influences on subsequent embryogenesis; iii) prospective randomized controlled trials; and implementation of biomedical engineering technologies to remove practical limitations of technical signature’s and individual personnel/clinic variability’s.  In addition, we have physically trained, conservatively >600 individuals how to vitrify oocytes.

III.  Interdisciplinary collaborations to investigate utility of microfluidics and contemporary/developing microscopy for gamete/embryo isolation, manipulation, culture, and bioanalysis.  These studies focus on testing the potential use and/or benefit of using microfluidics and Raman microscopy to: i) overcome practical shortfalls of current ARTs, ii) provide capabilities currently not possible at a macro-scale; iii) to test benefits of biomimetics; iv) gain mechanistic insights in gamete/embryo development.

 IV.  Basic, translational, and applied studies to improve semen cryopreservation, semen/sperm analysis, and inhibition of sperm function. Spermatology is many timed overshadowed by a focus on female fertility, yet there are numerous areas of semen/sperm manipulation/analysis that can/should be investigated to improve fertility or inhibit fertility in light of contraception.  Recent collaborative physiological studies on body composition, metabolic syndromes, sperm function, and fertility are especially rewarding.

V.  Deriving and using human embryonic stem cells (hESCs) for greater understanding of: i) early developmental events; ii) pathophysiology of single-gene defect disorders; and iii) integrating bioengineering technologies to solve practical problems in stem cell growth, differentiation, organoid formation, and translational/clinical trial utility.  Our collaborative research goals are to produce hESCs that are disease specific, sometimes genetically linked, acquire NIH registry acceptance, and initiate across-department and interdisciplinary projects that can eliminate existing research boundaries, barriers, or limitations and result in transformative discoveries to improve human health. 


PhD - Washington State University

Published Articles or Reviews

  1. Salari S, Adashi EY, Keller L, Johnson TRB, Smith GD. Human embryo donation for human embryonic stem cell derivation. Fert and Steril (2023) 119:3-10, PMID: 36494202.
  2. Ren Y, Yan Z, Yang M, Keller L, Zhu X, Lian X, Liu Q, Li R, Zhai F, Nie Y, Yan L, Smith GD, Qiao J. Regional and developmental characteristics of human embryo mosaicism revealed by single cell sequencing. PLOS Genetics (2022) 18(8):e1010310, PMID: 35939513.
  3. Cloutier M, Kumar S, Buttigieg E, Keller L, Erliandri I, Lee B, Williams A, Mojica-Perez S, Monteiro Da Rocha A, Smith GD, and Kalantry S. Preventing erosion of X-chromosome inactivation in human embryonic stem cells. Nature Comm (2022), 13:2516, PMID: 35523820.
  4. Kushnir VA, Smith GD, Adashi EY. Future of IVF: the new normal in human reproduction. Reprod Sci. (2022) 29, 849–856. PMID 34981459.
  5. Cantatore C, George JS. Depalo R, DAmato G, Moravek M, Smith GD. Vitrification of mouse oocytes with and without dimethyl sulphoxide: Influence on cryosurvival, development and targeted imprinted gene expression. J Assist Reprod Gen. (2021) 38, 2129–2138. PMID 34021463.
  6. Shahbazi MN, Wang T, Tao X, Weathersbee BAT, Sun L, Zhan Y, Keller L, Smith GD, Pellicer A, Scott RT, Seli E, Zernicka-Goetz M. Developmental potential of aneuploid human embryos cultured beyond implantation. Nature Comm (2020) 11-3987: 1-15. PMID 32778678
  7. Moore LR, Keller L, Bushart DD, Delatorre R, Li D, McLoughlin HS, Costa MDC, Shakkottai VG, Smith GD, Paulson H. Antisense oligonucleotide therapy rescues aggresome formation in a novel spinocerebellar ataxia type 3 human embryonic stem cell line. Stem Cell Res. (2019) 39:1-13. PMID: 31374463.
  8. Haenfler JM, Skariah G, Rodriguez CM, da Rocha AM, Parent JM, Smith GD, Todd PK. Targeted reactivation of FMR1 transcription in fragile X syndrome embryonic stem cells. Fron Mol Neurosci (2018) 11: 282. PMID: 30158855.
  9. Borges BC, Garcia-Galiano D, Cruz-Machado SS, Han X, Gavrilina GB, Saunders TL, Auchus RJ, Hammoud S, Smith GD, Elias CF. Obesity-induced infertility in mice is associated with disruption of epididymal Crisp4 and sperm fertilization capacity. Endocrinology (2017) 158: 2930–2943.  PMID: 28911169
  10. Rocha AM, Guerrero-Serna G, Helms A, Luzod C, Mironov S, Russell M, Jalife J, Day SM, Smith GD*, Herron TJ* (*corresponding authors). Deficient cMyBP-C protein expression during cardiomyocyte differentiation underlies human hypertrophic cardiomyopathy cellular phenotypes in disease specific human ES cell derived cardiomyocytes. J Mol Cellular Cardiology (2016) 99:197-206.  PMID:  27620334.
  11. Jasensky J, Boughton AP, Khmaladze A,Ding J, Zhang C, Swain JE, Smith GW, Chen Z, Smith GD. Live-cell quantification and comparison of mammalian oocyte cytosolic lipid content between species during development, and in relation to body composition using nonlinear vibrational microscopy. Analyst (2016) 141:4694-4706. PMID: 27272931
  12. Lai D, Ding J, Smith GW, Smith GD, Takayama S.  Slow and steady cell shrinkage reduces osmotic stress in bovine and murine oocyte and zygote vitrification. Hum Reprod (2015) 30:37-45.  PMID:  25355589.
  13. Rocha AM, Ding J, Slawny N, Wolf AM, Smith GD.  Loss of glycogen synthase kinase 3 isoforms during murine oocyte growth induces offspring cardiac dysfunction.  Biol Reprod (2015) 92:127-139. PMID: 25833158.
  14. Heo YS, Cabrera LM, Bormann C, Shah CT, Takayama S, Smith GD.  Dynamic microfunnel culture enhances embryo development and pregnancy rates. Hum Reprod (2010; Cover Article) 25:613-622. PMID: 20047936
  15. Villa-Diaz LG, Nandivada H, Ding J, O’Shea, KS, Lahann J, Smith GD.  Synthetic polymeric coatings for long-term maintenance of undifferentiated human embryonic stem cell growth.  Nature Biotech (2010) 28:581-584. PMID: 20512122.
  16. Acevedo NA, Ding J, Dunn R, Smith GD. Insulin signaling in mouse oocytes. Biol Reprod (2007) 77:872-879PMID: 17625112.

A full list of publications can be found at: is external)

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