Smith Research Program

Contact information: James Smith, MD, MS
[email protected]

Funding:  Department of Urology, NIH, UCSF


Dr. Smith’s principal research interests center on cancer, fertility preservation, and cancer treatment effects on male reproductive biology. In collaboration with several other researchers, Dr. Smith seeks to answer questions in several keys areas:
1.  Mechanism and Regulation of Sperm Motility
Men treated with chemo- and radiation therapy for cancer often suffer from significant declines in sperm concentration or motility, key measures of sperm function. In this collaboration with Dr. Polina Lishko, a faculty member in the UC Berkeley MCB Department, we are exploring the functional properties of human sperm at different stages of their development using the “Sperm Patch Clamp” technique. This technique allows for measurement of current through sperm membrane ion channels. We have identified several novel promoters and inhibitors that regulate these channels. With this approach, we seek to better understand the effect of cancer treatments on functional properties of sperm.

2.  Tyrosine Kinase Inhibitor Study
Tyrosine kinase inhibitors (TKI) are a targeted class of cancer treatments that offer many cancer patients new ways of fighting their disease. In collaboration with Dr. Lishko, this prospective study of men receiving TKI will evaluate the fertility effect of this targeted cancer treatment on semen analysis properties along with its potential for inhibition of sperm functional characteristics. Recruitment began November 2012.

3.  Identification and Differentiation of Spermatogonial Stem Cells
Differentiation of SSC to mature sperm has been demonstrated in model animal systems. No study has yet successfully developed this capability in humans. This approach offers potential as a treatment for men left without sperm after cancer treatment. Collaborating with Dr. Nam Tran, we seek to: 1) Identify SSC from fresh and cryopreservedsamples using immunohistochemistry and FACS techniques; 2) Induce in-vitro differentiation of SSC to early meiotic sperm cells; 3) Induce meiotic cells to mature into spermatozoa.

4.  Costs of fertility care
In studies based on retrospective and prospective cohorts of patients seeking fertility care, in collaboration with Dr. Patricia Katz of the Institute for Health Policy Studies, Smith continues to explore the utilization of fertility care, out-of-pocket fertility expenses, time costs associated with fertility care, and socioeconomic disparities couples face when seeking reproductive health care.