In this post you'll find pointers to the profiles of some of the SENS Research Foundation summer scholars for 2015. These talented young scientists are placed in influential labs for the summer to work on research relevant to the goal of treating aging and age-related disease. Cultivating today's young academics is the starting point for building the dedicated, enthusiastic research community of tomorrow, the people who will usher in the rejuvenation therapies of the 2030s and beyond.
At the very best possible pace of development, a pace that would require considerably more funding for the relevant research than is presently the case, it will likely be another twenty years before the first comprehensive package of rejuvenation therapies are in the final stages of development, on the way to the clinic. Unless the funding situation dramatically improves in the next few years, the likely timeline is longer: most of today's research interest in the treatment of aging as a medical condition goes towards research programs that cannot possibly produce actual rejuvenation, and can at best only modestly slow the pace of aging. Yet the cost in time and money for that course will likely be much greater than for attempts to create rejuvenation by repairing the causes of aging. It is frustrating, one of many things that must change if we are to see meaningful progress towards an end to aging.
The people who will lead laboratories and found startups at the time of the first commercial rejuvenation treatments are in the final years of their academic biotechnology studies today. Whether or not tomorrow's leaders choose to enter the aging research field is something that we can influence today. For many decades aging research has been the poor cousin in medicine, thought of as a dead-end, ill-funded area of research. Yet this is far from the case: aging research today is a hotbed of cutting-edge molecular biology, rich with potential, and I think it no great exaggeration to say that medical control over degenerative aging will grow to become the principal pillar of medicine in the later decades of this century. There are names and fortunes to be made in the years ahead, but that all starts with education: showing the students of today that work on aging is a great choice for a life science career, and helping them to make connections in the research community and related industries that will serve them well in the years ahead.
As for any human endeavor, a research community doesn't just spontaneously emerge from nothing. It must be cultivated. This is an important aspect of the work of organizations like the SENS Research Foundation. It's not just a matter of funding and coordinating the right research today, but also ensuring that a community of enthusiastic scientists exists to carry that work through to completion in the decades ahead. Thus the SENS Research Foundation runs a yearly placement of talented young scientists in their Summer Scholars program, sending them out to some of the most noted laboratories in the US. Some of this year's crop are profiled:
I am very excited to work for SENS Research Foundation because I will have the chance to learn and contribute to research centered around the diseases of aging at the Wake Forest Institute for Regenerative Medicine (WFIRM), which is an extraordinary place for this field. This summer, my Principal Investigator is Dr. Graça Almeida-Porada and my mentors are Saloomeh Mokhtari and Steven Greenberg. Our goal is to develop novel cell-based therapies that could provide a curative treatment for Inflammatory Bowel Disease (IBD).
The Almeida-Porada lab has already shown that increasing the expression of immunomodulatory molecules on mesenchymal stem cells (MSC) leads to better immunosuppression and improvement of IBD in a murine model. Other cells that could help in the treatment of the gut inflammation are endothelial progenitor cells (EPC). These cells are known to increase the vascularization in ischemic tissues. Therefore, EPC could help normalize vascularization in the intestinal submucosa of IBD patients. Hence, I plan to treat IBD in mice using MSC and EPC as cell therapy to promote the modulation of the immune system and increase the vascularization in the intestine.
I first became interested in the field of regenerative medicine after viewing Dr. Anthony Atala's TED Talk on his 3-D kidney printing work. The ability of regenerative medicine to be applied to a vast array of cells, tissues, and organs and the possibility of making patients truly well again, as opposed to managing symptoms, is inspiring. WFIRM is an outstanding research institution, and it is an honor to have been selected to spend the summer learning and growing here.
This summer, I am working under the direction of Dr. John Jackson to generate thymus organoids capable of producing functional T-cells. The thymus serves an important function as the site of T-cell development. Interestingly, as we age, the thymus undergoes involution, or decreases in size, leading to a decrease in naïve T-cells. The ability to generate a functional thymus outside the body would have a number of clinical applications, including rejuvenation of an aging thymus to boost the immune response in older individuals and development of tolerance in organ transplantation.
This summer, I will be conducting my research project in Dr. Jeanne Loring's laboratory at the Center for Regenerative Medicine in the Scripps Research Institute. The Loring lab has derived dermal fibroblasts from 10 patients with Parkinson's disease. These fibroblasts have been reprogrammed to induced pluripotent stem cell (iPSCs), which have been differentiated into midbrain-specific neural progenitor cells. These cells will later develop into dopaminergic neurons after transplantation. The Loring lab is the first lab conducting iPSC transplantation on Parkinson's disease patients, so it is essential to ensure genomic stability of the cells being transplanted. An important method to determine genomic integrity of patients' iPSC lines is single nucleotide polymorphism (SNP) genotyping, which can be used to examine millions of single base pair differences at genomic sites specific to humans.
SNP analysis will enable me to determine if the cell populations are suitable for transplantation or whether they have too much genetic change and, hence, potential risk for tumorigenesis. My research this summer will generate and analyze genomic SNP profiles from patient-specific dermal fibroblasts, iPSCs, and neuronal progenitors. SNP patterns from the three cell types will be compared to determine whether genomic instability has occurred from fibroblasts to iPSCs then to neuronal progenitors. Hopefully, with efforts from other scientists and me, the Loring Lab will successfully identify some cell lines that are suitable for transplantation and pass the FDA approval.
Under the mentorship of Professor Chas Bountra and Dr. David Brindley, my project will propose a model of open innovation in the translation process to address the problem of developing Alzheimer's disease drugs. To do this, I will use a model to compare open innovation to more conventional drug development strategies by measuring certain metrics to determine the effect open innovation has on each stage of the translation process. These metrics can give us an insight into the rate and effectiveness of the process at each stage and, therefore, an idea about how open innovation can improve the translation process.
We are all familiar with Alzheimer's disease. Not only is it a disease that causes significant morbidity and mortality, it is also one of the most costly. So, why haven't we cured it already? There are numerous reasons why this is a difficult problem to solve. The main problem being the lack of understanding of the disease itself, including potential drug targets. This leads to drug discovery being very risky and inefficient. For example, in the last few decades, extensive research has explored targeting amyloid plaques and neurofibrillary tangles as potential drug targets to treat Alzheimer's disease with little success. Furthermore, in the conventional drug development process, organizations work in isolation, creating an environment in which similar compounds are sometimes studied in parallel. So, how can we fix this problem? The answer lies in making the translation process between research and healthcare implementation more effective.
This summer, I will be working in Dr. Anthony Atala and Dr. James Yoo's lab under Drs. Myung Jae Jeon and Young Sik Choi studying ovarian cell therapies that will be able to produce natural levels of sex steroids that can be controlled by feedback mechanisms and, hopefully, produce viable oocytes. The importance of this research is providing effective therapies for hormone and egg replacement that do not have the potential harmful side effects, such as increased risk for heart disease and certain cancers, that current replacement methods pose. Cell-based therapies can be used in post-menopausal women, women who have had ovarian cancer, and women who have experienced damage to their ovaries from other sources.
Currently, we are characterizing a 3D collagen matrix and structure that closely mimics the natural environment within the ovary. My specific role in the project will be to test and define the importance of the ratio of granulosa cells to theca cells as well as find the optimum total number of cells in each follicle construct. I will be analyzing each ratio and follicle size for the ability to produce a physiologically normal level of estrogen and progesterone as well as assessing overall cell viability.
At the SRF Research Center, I am working on the Oncology team with Dr. Haroldo Silva. My project is to develop new high-throughput assays for quantifying activity of the Alternative Lengthening of Telomeres (ALT) pathway in human cells. Cancer cells must be able to proliferate without limit - something that normal cells can't do. Telomeres are repetitive noncoding DNA strands at the ends of eukaryotic (plants, animals, etc.) chromosomes. Every time a cell divides, telomeres shorten, protecting the genetic material from being damaged and limiting the proliferation of the cell. Some cells, such as stem cells and cancer cells, are able to lengthen their telomeres to be able to divide without limit. 85% of cancer cells use the enzyme telomerase to lengthen telomeres. The remainder maintain telomere length with ALT, a pathway based on homologous recombination (a mechanism used for DNA repair).
The current assays for ALT activity rely on characteristics of ALT cells: heterogeneous telomere length, the presence of ALT-associated PML bodies (APBs), and the presence of extrachromosomal circular C-strand telomeric DNA (C-Circles, or CCs). All of the current assays have problems, and none of them are high-throughput. One of the assays I'll be developing is a high-throughput version of the APB assay. Classically, this assay measures colocalization of PML protein with TRF2, a telomere binding protein (drug treatment can lower TRF2 expression, making the APB assay unreliable). I will bypass TRF2 and look for colocalization of PML with telomeric DNA directly. I'll accomplish this by using immunofluorescence to detect PML protein and FISH (fluorescent in situ hybridization) to detect telomeric DNA with a complementary fluorescent DNA probe.