Garcia Research Program

Garcia Research Program

Optimizing Radiotherapy Targeting for Invasive Bladder Cancer

The U.S. population is, on average, living longer than ever before. As people with chronic diseases live longer, many are presenting with muscle invasive bladder cancer at advanced age, when they are less fit to undergo radical cystectomy (removal of the bladder with urinary diversion using a segment of one's own intestine to either create a urostomy (urine drainage to a urine collection bag at the affixed to the abdominal wall, or, creation of a neobladder (bladder replacement)...

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Sperm Selection for IVF/ICSI

Utilization of assisted reproductive technologies (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (IVF-ICSI) is increasing annually both in the U.S. and all industrialized countries worldwide. ART is associated with several-fold higher twin/multiple-gestation pregnancies, which is driven by transfer of multiple embryos during ART cycles, to help ensure that at least one live-birth results following transfer. There is also growing evidence that ART is associated with a statistically significant increase in the incidence of congenital malformations among offspring.

Sperm selection remains entirely subjective, and, there is no way to predict sperm quality at selection. Also, during ART, when sperm motility within a semen sample is limited or absent, it is virtually impossible to predict the viability of sperm; selection of significantly damaged results in ART failure and likely risks the health and viability of offspring.   

Dr. Garcia’s lab has was the first to propose the use of Optoelectronic Tweezers (OET), a light-induced, dielectrophoresis (DEP)-based technology wherein live cells are spontaneously attracted to dielectrophoresis fields generated by patterned light incident upon two specialized chips separated by a 200 micron gap. Dead cells are entirely neutral to the DEP field. Dying cells are very weakly repulsed by the DEP field. When a suspension of sperm is placed between our two OET chips, DEP fields can be projected and moved about within the suspension, under microscopy, to identify viable sperm cells independent of sperm motility.  In this way, a viable non-motile sperm can be distinguished from among millions of sperm within seconds. We hypothesized that if a cell’s attraction to the DEP field predicts a binary outcome absolute cell quality – whether it is alive or dead, then, relative attraction could predict relative cell quality, to distinguish a healthier cell from a less healthy one. cell . In our preliminary work, we have shown that human sperm respond to OET just as mouse sperm do, and, using vital cell assays, that OET predicts human sperm viability in vitro. We have also shown that OET sperm assay is compatible with sperm viability to produce live, healthy mouse pups. Lastly we have also shown that the magnitude of an individual sperm’s attraction to the OET field predicts its likelihood of resulting in a healthy, live birth. We have also shown that the OET assay we developed is compatible with assay of preimplantation mouse embryos, which result in normal birth rates of healthy pups following OET assay. We hypothesize that OET could be used to predict both sperm and preimplantation embryo quality before ICSI and embryo transfer. The assays and technologies we have developed have U.S. Patents-Pending, and have been licensed to a biotech company.  Dr. Garcia was awarded an NIH K08 Award to pursue further research with OET for sperm and embryo selection for IVF/ICSI.

 

Developing Bladder Fiducial Markers