My name is Ali Hamandi, and I am a rising senior at Penn, majoring in neuroscience and minoring in chemistry. In the Spring of my junior year at Penn, I began working in Dr. Li Shen’s lab at the Perelman School of Medicine exploring the heterogeneous etiology of Alzheimer’s Disease. Through the STEER program, I have been able to continue this work over the summer and expand both my knowledge in the subfield and the scope of my research project to include the influence of environmental factors on AD. 

What is your summer research project?

The primary goal of my summer research project has been to elucidate the association between environmental factors and specific single nucleotide polymorphisms correlated with specific presentations of Alzheimer’s Disease. My work relies on massive data banks collected through the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and other collaborating projects, which include longitudinal data concerning cognitive, biomarker, and imaging data of Alzheimer’s patients and patients with mild cognitive impairment (MCI) at risk of developing AD. Environmental factors of interest include the gender of patients, their level of education, and whether they abide in the status of MCI or develop AD. 

What are the implications of your research?

The overall goal of my research is to better differentiate how different genetic-environmental causes lead to the different constellations of symptoms which are aggregated under the label of Alzheimer’s Disease. AD is likely heterogeneous in nature and is not widely acknowledged as such due to a lack of understanding of the variety of causal mechanisms underlying it. Elucidating different causal mechanisms for AD can ultimately lead to the development of more targeted therapies against the disease and early detection protocols based around screening procedures and a holistic profile of each individual patient’s history of environmental exposures which place them at risk. 

What new skills have you gained through your research? 

Through my time at the Shen Lab, I learned how to work with massive data structures and how to conduct Genome Wide Association Studies (GWAS) using specialized software. I also developed a keener understanding of contemporary literature on Alzheimer’s Disease and the various theoretical frameworks scientists have developed to aid its diagnosis and the detection of strongly associated genetic and environmental factors on the incidence of Alzheimer’s Disease. Through my time in the STEER program, I have been able to widen my scope of my exploration and to deepen my research experience.

What is your summer research project? 

My summer research project involves quantifying the rate at which amyloid beta proteins aggregate. Amyloid beta proteins form plaques in the brain when they aggregate, which disrupts neural connections and cellular communication. As such, my project involves preparing amyloid beta protein in order to have it fibrilize and observe the rate at which it does so. This is done through the usage of a stain, Thioflavin T, and a fluorescence spectrometer. Thioflavin T specifically binds to amyloid beta fibrils but not the monomer, and when it binds to the fibrils its fluorescence increases dramatically. As such, by observing how the fluorescence increases over the course of the incubation period we can measure how quickly the proteins aggregate. I will also be looking into how HNE, 4-Hydroxynonenal, affects the rate of fibrilization by adding it in various concentrations to the amyloid beta samples. 

What are the implications of your research? 

The true cause behind Alzheimer’s and the aggregation of amyloid beta proteins in the brain is still not fully understood, but the two seem to be related. As such, by understanding how and why amyloid beta proteins aggregate, we may be a step closer to creating better treatments for Alzheimer’s Disease. HNE is important as it is formed from the oxidation of omega-6 polyunsaturated fatty acids, a molecule we find in our brains and foods thought to be healthy for humans. If it definitively speeds up the rate of amyloid beta aggregation then it may be a factor behind what leads to Alzheimer’s Disease.

What new skills have you gained through your research?

My research experience has been an incredible introduction to all the equipment in a laboratory, which I have not worked with before. This includes using pipettes, plasma cleaners, lyophilizers, and much more. I learned how to use machines such as a spectrophotometer and fluorescence spectrometer as well, which often introduced challenges for me as I ran into a multitude of minor troubleshooting issues. It forced me to think creatively in order to master the software and understand how the machine properly operates. Furthermore, I improved at searching for and comprehending scientific papers, which was important as I had to plan how to prepare the amyloid beta fibrils by looking through previous literature.

My name is Henry Nick, and I am a rising junior at Penn. I am majoring in Neuroscience with minors in Chemistry, Sociology, and Cognitive Science. This summer, I was lucky to be matched with Dr. Sigrid Veasey and her lab in the Center for Sleep and Circadian Neurobiology to examine the effects of sleep fragmentation and orexin loss on inflammation of the brain.

What is your summer research project? 

This summer, my primary project sought to explore the effects of sleep fragmentation and loss of orexinergic neurons on the health and wellbeing of the brain. Under guidance and mentorship from Dr. Veasey and the peers and colleagues in her lab, I have been able to analyze hippocampi from multiple groups of mice – rested wild type, sleep fragmented wild type, rested orexin knockout, and sleep fragmented orexin knockout – to determine if sleep fragmentation causes an enhanced proinflammatory response in brains when orexinergic neurons – neurons that determine whether an animal should be asleep or awake – are not active. 

What are the implications of your research? 

Sleep fragmentation occurs when there are frequent, abnormal awakenings during the sleep-wake cycle, disrupting the natural sleep cycle. Artificial lighting, longer work commuting times, night-shift work, and increasing availability of computers and televisions have all contributed to shortened sleep times, and is especially common in more densely populated inner city environments, where all of these are more common. These interruptions cause negative impacts on cognitive performance; including mood, attention, memory, and executive function.

Lack of sleep causes a loss of orexin neurons which causes systemic inflammation in monocytes. Monocytes are a type of white blood cell produced in the bone marrow. They fight infections and remove dead or damaged cells and fight cancer cells. Orexin is a neuropeptide that regulates various physiological phenomena such as wakefulness, feeding, reward, and thermogenesis. The body energy level influences orexin neuronal activity to coordinate arousal and energy homeostasis. Loss of orexin signaling has been linked to narcolepsy, obesity, and age-related disorders caused by reduced energy expenditure, reduced food intake, and weight loss.

What new skills have you gained through your research? 

It was a nice change of pace to be able to conduct in-person research this summer through the STEER program coming out of a long period of remote work. My research relied on examining mouse brains, so I had to go through a rigorous training protocol in order to ensure I was adequately trained to work with animals. This taught me a lot behind the ethics of research which I know will be a lifelong skill. Within the lab, I focused on immunohistochemistry, which provides researchers with a window into inflammation. This staining technique uses antibodies conjugated to enzymes that catalyze reactions to form detectable compounds to visualize and localize specific antigen markers in a tissue sample. I was unfamiliar with this entire process prior to STEER but had to go through it multiple times this summer since I was looking for a whole array of protein markers. I was grateful to have this opportunity to build my wet lab and animal handling skills which I know I will use a lot in the future.

What is your summer research project?

I was drawn to the topic of wildfires because while they are an extremely common and natural occurrence, they have become far more frequent and threatening to both human and animal life in the recent years, with multitudes of research pointing to anthropogenic climate change as the reason behind this. Moreover, while a lot of data has emphasized the effect of wildfires on physical/respiratory health, there is much less on that of wildfires on mental health. Under the mentorship of Dr. Hwang, I used R to investigate the connection between poor mental health days (dependent variable) and several fire indicators, such as percent risk of fire damage, PM2.5, poor AQI days, etc (independent variables). The figure that is attached shows that there is a positive correlation between bad mental health and increased risk of wildfire damage – a relationship that is more prominent when variation due to poverty level as well as education is removed. 

What are the implications of your research?

My methods and project was fairly straightforward and simple in its design. I think similar or more advanced models could be used to make great strides in health monitoring and improving treatment for populations that are most strongly disadvantaged by climate change, because comprehensive health services (including mental health services) are significantly more inaccessible to subgroups facing climate disasters in regions that are less equipped to treat human health and recover following major environmental events. 

What new skills have you gained through your research?

At the start of this program, I was definitely very unfamiliar with statistical analytics, and essentially all programming languages. While I would consider myself a beginner still, I have gained a lot more experience working with large quantities of data in R, and because I have spent all past research summers in a physical wetlab, I’ve also become more comfortable with the remote, computer-based side of research. Finally, I learned a lot about how to present data and explain statistically significant results to an audience of my peers and mentors. 

My name is Meg Gladieux, I am going into my third year at Penn, and I am a double major in Cognitive Science and French and Francophone studies. My academic and research interests lie in children’s development, particularly in how environmental influences shape cognitive development and implications for social policy. This summer, I worked with Dr. Jianghong Liu, whose research focuses on early childhood exposures and brain and behavioral outcomes in children and adolescents.

What is your summer research project?

My summer research focused largely on an independent literature search that integratively examined the current work in the fields of community and environmental health regarding cumulative outcomes of toxic environmental exposures and social disadvantage on children’s cognition. I examined journal articles across several databases to understand the current state of the field and to identify gaps in understanding of this very important dimension of community health. Through this process, I particularly concentrated on two key environmental exposures: air pollution, including PM2.5, PM10, and PAH, and lead exposure. I also analyzed a few recent publications dealing with secondhand tobacco smoke as well as other common household toxicants affecting children, including pesticides and PBDE. I focused on these exposures because they are the most prevalent exposures in children, with high risk in children’s environments through nearby industrial sites, heavily trafficked areas, homes, particularly homes with older infrastructure, schools, and other buildings and background exposures. 

I cross-searched these key childhood sources of toxic exposure with multidimensional indicators of adversity including material hardship, parental education, family dynamics, socioeconomic status, neighborhood conditions, and exposure to violence and trauma. While independently each toxic physical exposure and social exposures are associated with adverse cognitive outcomes, particularly relating to school performance, recent studies seem to indicate a cumulative effect when children encounter both types of environmental exposure. I developed a framework for thinking about cumulative environmental exposures within different domains of children’s holistic environments. The magnification of negative cognitive outcomes for children experiencing both environmental toxicity and social adversity is through prolonged toxic stress, in which there is a prolonged stress reaction in the brain due to both external biological and psychosocial factors and internal autonomic stress responses to the external world. These prolonged stress responses interfere with healthy cognitive development, increasing the likelihood of cognitive difficulties in childhood and beyond. 

What are the implications of your research?

Thinking about policy and practical implications was a really big part of my work this summer. It’s important to systematically collect evidence that a problem exists, but ultimately, the goal of research is to figure out ways to solve problems. If we know that children facing more adversity and hardship are at higher risk of toxic environmental exposures and that these exposures actually amplify the negative effects of one another, it becomes even more vital to protect these vulnerable children from these risk factors both in their physical environments and social environments. The mechanism for the relationship between physical and psychosocial exposures contributing to toxic stress is multifaceted and still poorly understood. It is associated with neurotransmitter disruptions and inflammatory responses that hinder brain development. In fact, in MRI studies, we can see physical differences between the brains of children who have experienced high levels of toxic stress and those who have not. 

This ultimately demonstrates that not only are vulnerable children more likely to be encountering the toxic environmental exposures, but their adverse social environments actually make the impact of those environmental exposures worse. Environmental pollution and overall climate change are having the biggest effects on disadvantaged communities, particularly the children within them. Mitigation of environmental hazards is thus most vital in the most poverty-stricken communities. Improving building infrastructure, increasing educational initiatives, and preventing further air and lead pollution from industry and construction through policy are possible first steps. Ultimately, protecting children through cultivating safe and loving holistic environments is the best way to ensure healthy development. Several promising recent papers suggest that increasing support within schools for children at high risk for exposure to toxicants in their homes and neighborhoods and increasing access to safe greenspaces may act as protective mechanisms that mitigate the impact of toxic stress (McCrae et al., 2021; Aerts et al., 2018).

What new skills have you gained through your research?

This summer, I didn’t only have the opportunity to work on my own independent project, but also contributed broadly to much of my mentor’s other work and ongoing projects. In addition to developing my own critical thinking skills, independent thought, and creativity in scientific inquiry, I have also been able to take part in several other projects through supporting roles. I have helped edit several manuscripts and prepare them for publication. I have also gone through the process of submitting several papers to journals as well as making edits and addressing the comments of peer reviewers. Additionally, I have been able to support my mentor in preparing peer reviews and providing suggestions on other manuscripts that are in production related to environmental and community health. These experiences gave me invaluable insight into the overall research process beyond data collection, inquiry, and literature review.

Through my research and overall experience in STEER this summer, I feel that I have gained so many skills that I will carry with me throughout my education, into further research, and toward my future career. I have become skilled at literature synthesis as well as citation management. I have learned how to take a collection of papers and draw connections across them to find new insights and identify current gaps within the current field. I have also become extremely proficient in navigating databases and sorting through extensive libraries of research to pick out the articles that are the most relevant to the problem I am researching. Finally, I have learned a lot about community health and participatory action research in community environmental work. Especially in studying people and the real-life effects of their environments on their well-being, research must prioritize inclusivity of community needs.

I am Esha Srinivasan and I am originally from a suburb of Raleigh, North Carolina. I am a rising sophomore at the University of Pennsylvania where I am majoring in biochemistry and minoring in music. My after college plans include veterinary school! My love for animals and my experience with environmental science in high school made me really excited for the opportunity of being a STEER scholar. Lucky enough to spend the summer in Philadelphia, I worked in a translational human immunodeficiency virus (HIV) research lab with Dr. Katharine Bar. I found the summer to be extremely rewarding, considering how apt it is to study infectious pathogens in the midst of a global health crisis.

What is your summer research project?

This summer, I aided in the effort of understanding how HIV evolves in response to treatments and the body’s immune system. I sequenced SIVmac239, a close relative to HIV, in the plasma samples of 13 animals inoculated with the virus. The 13 animals were given antiretroviral therapy (ART) to suppress their viral load. Some animals were given monoclonal antibodies to prolong the suppression of the virus without having to continue ART.  After sequencing, I was able to look at the ambiguities between the original reference sequence and the viruses found within the sample. 

What are the implications of your research?

HIV is a health crisis ubiquitous throughout the world. Several millions of individuals are currently living with HIV globally. Though current medicines are certainly effective at suppressing the virus and prolonging the lives of patients, access to treatments unfortunately differ throughout the world. Not only is healthcare access unequal, but also clades of HIV endemic to Europe and the United States are more well studied than other clades of the virus. Studying all types of HIV assures that any treatments found benefit all that are infected with HIV and not just those infected with a clade native to an affluent country.

Since this research reveals the places in which HIV has changed its sequence, these loci on the HIV genome can help researchers understand how HIV is able to evade the body’s immune response. While ART is able to remove the virus lingering throughout the body, it is not able to remove the reservoir of virus that remains in the cells of the host. Understanding why HIV makes these changes brings us one step closer to finding a cure or preventative for the virus.

What new skills have you gained through your research?

Through this research, I was able to develop a deep appreciation for both the social science and actual science of HIV. Knowing about the debilitating effects this virus has on patients’ lives really motivates its research. I was also in awe of how clever HIV is at avoiding capture. I find it fascinating that a virus’ lack of skill in maintaining its own integrity actually supports its ability to persist in a host.

Gene sequencing was something that I had never done before this summer. At first it was daunting how the entire process seemed to consist of machines and tiny volumes of clear liquids, but it was motivating being able to make parallels between HIV’s replication and the lab methods. Working with SIV instead of HIV taught me how relevant non-human primate models are to research, and about how we are always working towards improving the accuracy of these models. I also enjoyed learning about SIV’s role in the environment and how HIV was once zoonotic. I learned how to turn RNA into DNA and it was fascinating to me that we were able to replicate a process that HIV already knows how to do. I learned how to use the polymerase chain reaction to make copies of DNA. I also learned how to perform gel electrophoresis and how it can be used to confirm the size of sequence fragments. Using software to read and analyze sequences was new to me as well. I always thought it was so cool that we are able to detect these sequences down to single nucleotides. I am excited to be able to use these skills in my science courses in undergrad and beyond.