Gary D. Smith, PhD

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

6428 MS I
1301 E. Catherine St.
Ann Arbor, MI  48109-0617

734-764-4134

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. 

Credentials

PhD - Washington State University

Published Articles or Reviews

1.    Acevedo NA, Ding J, Dunn R, Smith GD.  Insulin signaling in mouse oocytes.  Biol Reprod (2007) 77:872-879. PMID: 17625112.

2.    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.

3.    Heo YS, Cabrera LM, Bormann C, Shah CT, Takayama S, Smith GD.  Dynamic microfunnel culture enhances embryo development and pregnancy rates.  Human Reprod (2010; Cover Article) 25:613-622. PMID: 20047936

4.    Smith GD, Serafini PC, Fioravanti J, Yadid I, Coslovsky M, Hassun P, Alegretti JR, Motta EL.  Prospective randomized comparison of human oocyte cryopreservation with slow-rate freezing and vitrification.  Fert and Steril (2010) 94:2088-2095. PMID: 20171613.

5.    Bormann CL, Smith GD, Padmanabhan V, Lee TM.  Prenatal testosterone and dihydrotestosterone exposure alters ram testes development.  Reproduction (2011) 142:167-173.  PMID:  21493716.

6.    Heo YS, Cabrera LM, Bormann CL, Smith GD, Takayama S.   Real time culture and analysis of single embryo metabolism using microfluidic device with deformation based actuation.  Lab on a Chip (2012) 12:2240-2246. PMID: 22402469.

7.    Schwab KR, Smith GD, Dressler GR.  Arrested spermatogenesis and evidence for DNA damage in PTIP mutant testes.  Dev Biol (2013) 373:64-71.  PMID:  23063797.

8.    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.

9.    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.

10.  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.

11.  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.

12.  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

A full list of publications can be found at: http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/48574243

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