Exploring Research Advancements Made Possible by the 2023 Connection Grant

David Hersh, MD, has been hard at work to make maternal fetal surgery for myelomeningocele safer and more effective with robot-assisted surgery. Here’s what he has to say:

Over the past 6 months, Timothy Crombleholme, MD, Director of the Fetal Care Center at Connecticut Children’s, and I have been working extensively to prepare for our upcoming work with the fetal sheep model of myelomeningocele. After meeting with robotic experts at the Hartford Hospital Center for Simulation and Innovation (CESI), Dr. Crombleholme and I have engaged in a series of courses using the da Vinci robotic simulators housed at CESI.

Over time, we’ve become more comfortable and proficient with using the da Vinci robot. Next steps will include moving on from the simulator – instead, we will use an actual da Vinci robot to perform additional work in a lab setting, before ultimately initiating our work with fetal sheep.

Simultaneously, we have developed an Institutional Animal Care and Use Committee (IACUC) protocol, detailing the humane and ethical treatment of the animals that will be involved in our upcoming study. The IACUC protocol is currently being reviewed by the veterinary team at CESI, and we expect approval shortly. We look forward to continuing our work to improve the prenatal treatment of myelomeningocele, and we are so grateful to Connecticut Children’s Connection for their ongoing support!

Kelly Hawley, PhD, is working to develop a syphilis vaccine that will ultimately save hundreds of thousands of children’s lives. As you may remember, syphilis, a sexually transmitted infection caused by Treponema pallidum (Tp), poses a growing threat to pediatric health in Connecticut and the world. The alarming worldwide resurgence of syphilis underscores the urgent need for a vaccine with global efficacy. Here’s an update from Dr. Hawley: 

Our knowledge of the expression profiles of Tp’s entire repertoire of outer membrane proteins (OMPs) is essential to guide selection of candidates for vaccine studies. As a prelude to clinical studies, we have been working on a Tp-specific probe-based enrichment to ‘capture’ transcripts for OMP targets within total RNA extracted from skin lesions of experimentally infected rabbits.

In the initial six months of the project, we have obtained approval from the Institutional Animal Care and Use Committee for the proposed study. Additionally, we have designed the target-specific probes necessary to capture the transcripts of OMP targets for the state-of-the-art “OmpCapRNA” sequencing.

Synthesis of these probes was initiated, and we are currently awaiting their arrival. In an attempt to maximize the remaining six-month time period of the project, we have already experimentally infected the initial cohorts of animals to produce the three biological materials [(i) Tp extracted from testis, (ii) Tp-infected testis, and (iii) Tp-infected skin] to be explored with “OmpCapRNA” sequencing.

Furthermore, we have tested multiple RNA extraction methods on the biological specimens and are presently evaluating the integrity of the resulting RNAs. These data will allow for the selection of an extraction method which provides the highest quality RNAs and enhances the success rate of the “OmpCapRNA” sequencing”. The highest quality RNAs will be moved forward for production of the NGS libraries, “OmpCapRNA” sequencing and subsequent data analysis.

Dr. Hawley and Dr. Hersh are making the most of the generous funding and opportunities afforded to them by members of Connecticut Children's Connection. They also look forward to cheering on their colleagues who will be standing before Connection members at the 2024 Grant Selection Funding Event on April 2, 2024. On behalf of our amazing research scientists, we are so grateful for the support that helps fuel outstanding research projects that aim to change the landscape of pediatric care. It’s a thrill and a privilege to be counted as a partner in such exciting discovery. If you are interested in learning more about this exciting opportunity, please visit Connecticut Children's Connection online.