Joint Research Effort of Michelson Grantees Kicks Off the New Year in Australia

This February, a new Michelson Grant project will initiate at the University of Newcastle in Callaghan, Australia that will combine the efforts of two previous Michelson Grant recipients, Drs. Lee Smith and John Aitken. The project entitled “Development of nano pharmaceutical strategies for the sterilization of domestic cats and dogs” builds upon technologies developed in their previous projects while introducing new drug delivery technologies that are currently used in humans.

Within the male gonads (i.e. testes) are two cell types (Sertoli and Leydig) that are necessary for the maintenance of sperm development and maturation. Without the support functions of these two cell types, mature sperm cell pools would not develop, thus resulting in an infertile male. This new project aims to permanently disrupt both cell types by delivering a gene to Sertoli and Leydig cells that will cause cell death. The genetic payload will be delivered intravenously by a lipid sphere called a nanoparticle which protects the DNA inside until being internalized into the target cells. In order to target the nanoparticles to the Sertoli and Leydig cells specifically, nanoparticles can be designed to incorporate small peptide sequences on their surface that bind to receptors present on the target cells (i.e. FSH and LH receptors on Sertoli and Leydig cells) thereby adding a level of safety preventing the gene drug from being internalized by non-Sertoli and non-Leydig cells.

The introduction of genes into cells to treat human and animal disease is coming of age and has been primarily built upon the use of either viral vectors or nanoparticle technologies. The use of viral vectors requires the modification of the virus’s genome to incorporate the genes of interest to be introduced. The virus is then manufactured with this DNA inside. Viral vectors are limited in their ability to be modified to introduce targeting peptides on their surface as is needed in this project. In contrast, nanoparticles can be formulated with different ratios of the various lipid components that form the sphere that protects the DNA until it enters the cell. Because of this versatility of manufacturing, many interactions of the nanoparticle components and targeting ligands bound to the surface of the nanoparticle can be tested with ease.

We are looking forward to working with Drs. Smith and Aitken on this project over the coming years. This new use of nanoparticle technology in our research portfolio is exciting and a great complement to our viral vector projects underway. You can learn more about all of the projects that we’ve funded to date by visiting our Research Findings page.

In Pursuit of a Nonsurgical Sterilant: New Michelson Grant Project Underway at the University of Arizona

We are thrilled to announce that a new Michelson Grant-funded project pursuing a nonsurgical sterilant is underway! The study, led by Dr. Benjamin Renquist of the University of Arizona, is titled, “Enhancing the toxicity of GnRH- and bivalent-targeted RIP conjugates to induce sterility.” This is a continuation of another Michelson Grant-funded project that Dr. Renquist began in 2012 titled, “Increasing the circulating half-life of GnRH-RIP conjugates to improve in vivo efficacy.”

In their newly funded study, the Renquist team will continue their investigation of how to safely destroy gonadotropes. To put this project into context, it’s important to have an understanding of the hypothalamic-pituitary-gonadal (HPG) axis, which controls development, reproduction, and aging in all animals. At the very top of this reproductive cascade is a part of the brain called the hypothalamus, which secretes the peptide gonadotropin-releasing hormone (GnRH). Once it is secreted, GnRH travels to the anterior pituitary at the base of the brain, where it then binds to receptors on cells called gonadotropes. This binding stimulates the gonadotropes to release gonadotropins, which are hormones that travel in the blood stream to the gonads (testes in males, ovaries in females) that trigger the production of testosterone and estrogen. Testosterone release helps trigger spermatogenesis (sperm production) in males, and estrogen is released by growing follicles in females. These two processes, together known as gametogenesis, enable animals to sexually reproduce. When testosterone and estrogen levels in the blood become sufficiently low, the hypothalamus will be triggered to secrete more GnRH, and the whole process will start all over again.

If you visit our Research Findings page, you will see that nearly all of our funded projects involve targeting some part of the HPG axis, and you can see why this makes sense – if one can permanently stop any of the processes that are a part of this cycle, whether in the hypothalamus, the pituitary, or the gonads, one can effectively shut down the reproductive system for good. If this can be achieved non-invasively, we will be able to reach our goal of developing a nonsurgical sterilant for companion animals.

For decades researchers have been attempting gonadotrope ablation, but most have been unsuccessful in completely destroying these cells. Complete gonadotrope destruction will result in sterility, which is why gonadotropes are such an attractive target for our program. Initial findings from Dr. Renquist’s first Michelson Grant-funded project have shown that gonadotropes are resistant to targeted toxins, so in this new project the Renquist team will focus on enhancing the efficacy of internalized toxins. They envision that they will have an optimized cytotoxin ready for testing in mice by the end of this two-year study.

The Michelson Prize & Grants program has approved a total of 35 projects for funding since its inception in 2008 and has committed nearly $15 million to those projects. Every day, our investigators are getting closer to unlocking the key to permanent, nonsurgical sterilization in companion animals. We are proud to support their work and are grateful for their dedication to our cause!

New MPG Research Project Underway at Massachusetts General Hospital

The Michelson Prize & Grants in Reproductive Biology is happy to announce that a new research project has begun this month in the search for a nonsurgical sterilant for cats and dogs.

Patricia Donahoe, MD, and David Pepin, PhD, both of the Simches Research Center at Massachusetts General Hospital, have teamed up for a three year grant totaling $605,366 titled, “Single treatment with AAV9 Mullerian Inhibiting Substance as an ideal permanent contraceptive.” Dr. Donahoe, the Director of Pediatric Surgical Research at Massachusetts General Hospital, is a pioneer researcher of Mullerian Inhibiting Substance (MIS), a recombinant reproductive hormone. While much of her research in the past has focused on MIS uses as a treatment for ovarian cancer, she will now apply her expertise to the Michelson Prize & Grants mission.

Dr. Pepin, a trained reproductive biologist, joined the Pediatric Surgical Research Laboratories at Massachusetts General Hospital in 2011 as a Research Fellow and an Ann Schreiber Mentored Investigator. More recently, he joined the Harvard Medical School faculty in 2014 as an Instructor in the Department of Surgery. On this project, he will be working with Dr. Donahoe to engineer new peptide modifications of MIS and introduce them into an adeno-associated viral vector.

In response to the new project, Dr. Gary K. Michelson said, “We are delighted that Dr. Donahoe and Dr. Pepin, two leading experts in MIS, are taking their knowledge and applying it to the need for a nonsurgical, permanent sterilant for cats and dogs. This is a brand new approach for the Michelson Grants, and we can’t wait to see how their research progresses.”

The Michelson Prize & Grants in Reproductive Biology, funded through the generous contributions of Dr. Gary K. Michelson and Alya Michelson, has committed over $14 million in international research grants toward a nonsurgical sterilization method for dogs and cats. For more information about all Michelson grantees and their research, visit our Current Grantee Profiles and Research Findings pages.

New Year, New MPG Projects

As 2015 begins, the Michelson Prize & Grants in Reproductive Biology is happy to announce that two new projects have also recently begun!

John Lannutti, PhD, a Professor in the Department of Materials Science and Engineering at The Ohio State University, has just begun his project, a four-year grant totaling $409,327 titled, “Electrospun delivery to enhance the effectiveness of anti-fertility strategies.” Dr. Lannutti is a leading expert in the field of electrospinning, a new technology in the biomaterials community.

Additionally, David Mooney, PhD, a Core Faculty Member at the Wyss Institute for Biologically Inspired Engineering and the Robert P. Pinkas Family Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences, began work in November on a three-year grant totaling $731,567 for his project titled, “Infection-mimicking biomaterials for vaccination against gonadotropin releasing hormone (GnRH).” Dr. Mooney’s research is focused on the design and synthesis of biomaterials that regulate the fate of cells in the body.

With these new projects beginning, Dr. Gary K. Michelson said, “We are thrilled that Drs. Lannutti and Mooney have committed to applying their expertise and cutting edge techniques to the search for a single-dose, nonsurgical sterilant for cats and dogs. We look forward to seeing how their research progresses.”

The Michelson Prize & Grants in Reproductive Biology is a leader in providing international research grants for the sole purpose of finding a nonsurgical sterilization method for dogs and cats. Now entering its seventh year, the Michelson Prize & Grants, funded through the generous contributions of Dr. Gary K. Michelson and Alya Michelson, has committed over $13 million total in grant funding. For more information about all Michelson grantees and their research, visit our Current Grantee Profiles and Research Findings pages.

New Michelson Grant Projects Begin

The Michelson Prize & Grants in Reproductive Biology is excited to announce several new projects that are currently underway.

R. John Aitken, PhD, ScD, FRSE, a Laureate Professor of Biological Sciences at the University of Newcastle in New South Wales, Australia recently began his second Michelson Grant-funded project, a three-year grant totaling $516,377 titled, “Alkylated FSH peptides as mediators of germ cell depletion.” Dr. Aitken recently completed another three-year project funded by the Michelson Grants totaling $908,554.

Additionally, Prema Narayan, PhD, an Associate Professor in the Department of Physiology at the Southern Illinois University School of Medicine was recently awarded a three-year grant totaling $581,287 for her project, “Novel toxin conjugates for targeted ablation of LHR expressing cells to induce infertility.”

Earlier this year, Tatiana I. Samoylova, PhD, an Associate Research Professor in the Department of Pathobiology at the Auburn University College of Veterinary Medicine, began her second Michelson Grant-funded project, titled “Ablation of pituitary gonadotropes by DNA vaccine targeting GnRH receptor: Proof of principle study in mice.” This will be a two-year project totaling $328,698. Dr. Samoylova also recently completed another two-year project funded by the Michelson Grants totaling $412,106.

The Michelson Prize & Grants in Reproductive Biology team is encouraged by the commitment of these investigators to developing a single-dose, nonsurgical sterilant for cats and dogs.

The Michelson Prize & Grants program is funded through the generous contributions of Dr. Gary K. Michelson and Alya Michelson. Since its inception in 2008, the Michelson Prize & Grants has committed over $14 million in international research grants to approved projects in the field of nonsurgical sterilization. For more information about all Michelson grantees, visit our Current Grantee Profiles and Research Findings pages.