2012 SRF Summer Scholar Profile: Connie Wang

Connie is pursuing a double B.S. in Bioengineering and Business Economics and Management from the California Institute of Technology (Caltech).  She is currently in her third year of study. During her time at Caltech, Connie has engaged in a variety of research interests.  She has conducted plant genetics research to determine whether a strain of Mimulus was a distinct subspecies and also helped design an optical coherence tomography (OCT) system for use in retinal surgery.

In 2012, she participated in the SENS Research Foundation Summer Internship Program. During her time at the SRF Research Center in Mountain View, California, she developed microglial cell assays that helped lay the groundwork for studying the relationship between microglia, aging, and Alzheimer’s Disease.

2012 Project

“Approximately 5-12% of the brain consists of cells called microglia that act as the main immune cells of the central nervous system. In healthy brains, microglia perform various neuroprotective functions by removing protein plaques, sick neurons, and other pathogens via phagocytosis (the process whereby microglia actually engulf and devour unwanted debris) in addition to secreting cytokines and neurotrophic factors. These functions have implicated microglia as important factors in Alzheimer’s Disease (AD), the most common cause of dementia in the elderly, afflicting one in ten individuals over the age of 65 and nearly half of those over the age of 85.

Protein plaques appear to play a key pathogenic role in AD. But, as we age, the housekeeping abilities of microglial cells appear to weaken, putting the brain at risk. Disfunctional microglia in older people may be responsible for exacerbating the buildup of plaques and tangles.

To determine the precise relationship between aging, microglia and Alzheimer’s Disease, I sought to develop a set of procedures for measuring functional indicators of microglia health in mice. These indicators included oxidative burst (a process in which microglia release particles to degrade unwanted substances) and phagocytosis. Both methods of isolating microglia that were tested (3-column magnetic separation and a Percoll density gradient) worked. However, the cells isolated using the Percoll gradient were more adherent in culture. Further studies may be necessary to determine which method yields healthier microglia. However, cells isolated by either method successfully demonstrated oxidative burst and phagocytosis of live E. coli cells in my functional assays, which utilized a dye that fluoresces in the presence of reactive oxidative species and GFP-expressing bacteria, respectively.”

Figure 1.

Phagocytosis capability of microglia (C) was compared to that of lymphocytes (A) and untreated microglia (B) with fluorescent polystyrene latex beads (Sigma).

These procedures lay the groundwork for future studies to assess the performance of microglia at different ages and, thereby, come to a better understanding of Alzheimer’s Disease.

Future Plans:

This summer, Connie is working with the Reichert lab at Duke University to develop an angiogenesis-promoting system for glucose sensors planted under the skin with the goal of making them a viable long-term solution for insulin-dependent diabetics. She will return to Caltech in the fall to begin her final year of study before applying to graduate school in 2014.

2012 SRF Summer Scholar Profile: Sam Curran

Sam received his B.S. in Environmental Biology from The State University of New York (SUNY), College of Environmental Science and Forestry (ESF) in Syracuse, NY. As an undergraduate, Sam engaged in a wide variety of research projects. He investigated the bioconversion of renewable resources to useful end products in Dr. James Nakas’ microbiology laboratory. As a research aide in Dr. John Farrell’s SUNY ESF laboratory at Thousand Island Biological Station, he studied aquatic ecology and management of aquatic resources. In the summer of 2012 as part of the SENS Research Foundation Summer Internship Program, Sam joined Dr. Judith Campisi’s laboratory at the Buck Institute for Research on Aging to work on a project dealing with the senescence phenotype of mesenchymal stem cells:

Mesenchymal Stem Cell Senescence

“Mesenchymal stem cells (MSCs) are adult stem cells found in bone marrow, in fatty tissues, and around blood vessels. MSCs are important for wound healing, tissue regeneration, and immune suppression. Currently, multiple clinical trials are investigating whether MSCs can be used as treatment for diseases such as graft-versus-host disorder and rheumatoid arthritis.

While the senescence of MSCs and the harmful effect of the senescence-associated secretory phenotype (SASP) has been widely observed, little is known about the mechanisms and physiological implications of MSC senescence. My summer project involved studying the MSC senescence phenotype – in particular, the typical phenotypic markers of senescence: growth arrest, enlarged morphology, senescence-associated B-galactosidase expression, high levels of cell cycle inhibitors, and a SASP.

My project yielded a wealth of information about MSC senescence, which will serve as the foundation for future studies. I am already pursuing one implication from my studies. Immunofluorescence and western blotting experiments suggest that there may be multiple types of senescence in MSCs: one form that is an artifact of culture stress and a second, more physiologically relevant form that is a response to DNA damage.”

Figure 1.

Future Plans:

After the success of his summer project, Sam was invited by the Campisi lab to continue his research for a year of full-time funding by the SENS Research Foundation. Since his summer internship ended, Sam has made a number of novel discoveries. For instance, the SASP of MSCs may be different than other cells due to their immunosuppressive secretions. Sam has already identified one senescence-associated immunosuppressive factor that may be implicated in two important biological phenomenon: the ability of senescent cells to evade immune-surveillance and age-related decline of immune system function. Sam hopes to identify additional immunosuppressive MSC SASP factors with yet another year of funded research in the Campisi lab before pursuing a Ph.D. in bioengineering in the fall of 2014.

2012 SRF Summer Scholar Profile: Nick Schaum

Nick received his B.S. in Biological Sciences from Virginia Tech in May 2013. As an undergraduate, he worked in Dr. David Bevan’s molecular modeling laboratory studying the accumulation of amyloid beta, a protein that plays an important role in the development of Alzheimer’s Disease. While at Virginia Tech, Nick also worked with Dr. Rick Jensen on bioinformatics projects and an SRF literature review project focused on identifying single-nucleotide differences in DNA sequences (called SNPs), which are associated with aging.

During his internship last summer in the lab of Dr. Judith Campisi at the Buck Institute for Research on Aging, Nick worked with Dr. Albert Davalos researching ways to prevent senescent cells from promoting tumor growth.

2012 Project

“A senescent cell is a damaged cell that has stopped dividing because it was at risk of becoming cancerous. Senescence, therefore, is a naturally occurring form of cancer prevention. Chemotherapy works by targeting cancer cells to undergo cell death, but as a byproduct, induces senescence in non-cancerous cells. Unfortunately, senescence is a double-edged sword because senescent cells also secrete proteins that promote tumor growth in the surrounding tissue. To make matters worse, our research last summer suggests that the presence of normal, non-senescent cells may accelerate these harmful secretions from senescent cells.

Consequently, the goal of my project was to inhibit these harmful secretions while maintaining the beneficial aspects of cellular senescence.

After exploring several possibilities for achieving this, I found a specific class of small molecule activators capable of reducing nearly all secretions by senescent cells. It even worked on senescent cells whose state was induced by chemotherapy. Better still, the small molecule activators also kill cancer cells and are currently in clinical trials as chemotherapeutics.”

Future Plans:

Upon completing his summer internship, Nick was funded by SRF to study further methods of reducing the harmful effects of senescent cells at the Buck Institute. One such strategy involves analyzing the behavior of a protein called HMGB1. This work culminated in a manuscript on which Nick is an author. The article, published in the Journal of Cell Biology in May of 2013, described how inhibiting the activity of this protein prevented senescent cells from secreting harmful substances.

Nick continues to work on the SRF literature review project.

In September, Nick will begin graduate school at Stanford University in the Stem Cell Biology and Regenerative Medicine program.

2012 SRF Summer Scholar Profile: Ali Crampton

Ali will receive her B.S. in Biomedical Engineering from the University of California at Irvine in June 2013 after just three years of study. She worked in the Cardiopulmonary Transport and Tissue Remodeling Laboratory at UCI starting as a freshman, culminating in a project in her final year to develop a 3D in vitro model of human microvasculature for studying metastasis. During her 2012 summer internship with the MitoSENS team at the SRF Research Center in Mountain View, CA, Ali developed a method for detecting mycoplasma contamination, as she describes below.

2012 Project

“Mycoplasma is a bacterium that is a common contaminant in mammalian cell culture because it is difficult to detect by routine inspection. Since mycoplasma can alter cellular function, it is necessary to rigorously identify and remove signs of contamination. Working with the MitoSENS research team last summer, one of my goals was to devise a mycoplasma screening protocol that would monitor and identify contaminated samples. 

Using PCR-based commercial assays as a guide, I optimized an assay for identifying two common strains of mycoplasma.  I then found that some of our cell cultures were indeed contaminated.  This was not a problem, however, because mycoplasma contamination is treatable. The MitoSENS team implemented an antibiotic treatment for these cultures and continues to use my mycoplasma screening assay as a safeguard against further contamination.”

Figure 1.

Future Plans:

Ali returns to the SRF Research Center this summer to work on the problem of damage to mitochondrial genes. Mitochondrial genes are prone to damage from by-products of cellular respiration, which leads to a loss of cell function. Ali’s 2013 summer project will be to investigate two possible methods of supplying proteins to the affected mitochondria, in order to restore proper function. This fall, Ali will begin the next chapter of her career as a Biomedical Engineering graduate student at the University of Minnesota.

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