A fifth-year graduate student in the laboratory of A. James Hudspeth, M.D., Ph.D.

When sound waves enter our ear, they physically push on specialized cells that then get excited and signal their activation to the brain. Because these sensory cells are physically stimulated by sound waves, they need to be positioned properly within the tissues of the ear to function correctly.

Ms. Atlas is interested in understanding how organs like the ear develop with a high level of precision. This is an important question because the intricate structure of the ear is required for its proper function.

To answer these kinds of questions in a tractable system, she has turned to the model system of zebrafish, which have sensory organs embedded on the surface of their skin that contain cells very similar to the ones in human ears. The fish use these organs to sense water flows and thus escape predation, align with currents and school with other fish. Importantly, since these organs are on the surface of fish, it is possible to acquire long, high-resolution 3D videos of their development.

In the past year as a Fisher Fellow, Ms. Atlas has optimized imaging protocols and data analysis pipelines so that she can study cell movements and structure as sensory cells position themselves and interact with their neighbors. She has also optimized protocols in the lab to generate mutants using CRISPR-Cas9 and to assess gene expression changes as cells develop. These protocols will ultimately help to understand the machinery that cells use to interact with each other and to move around to create a tissue that functions properly. Ultimately, her work will help explain how cells use potentially basic, simple rules and work together to generate complex structures.

A fourth-year graduate student in the laboratory of Alipasha Vaziri, Ph.D.

For the past year, Mr. Barber has primarily been focused on establishing a training and behavioral analysis pipeline that will serve as the basis of his investigation into the neural mechanisms underlying decision- making.

Briefly, mice are trained to control the movement of a visual stimulus across an LCD screen by turning a steering wheel. Each trial begins with a stimulus appearing on either the left or right side of the screen. Mice are motivated to guide the stimulus to the center of the screen to receive a reward. Mr. Barber and his colleagues can vary stimulus strength (i.e. the level of evidence supporting a choice) and stimulus frequency (i.e. how often a certain type of evidence is provided) to test how these external factors influence the decisions of the mouse. This paradigm is used as a system to track decisions in a controlled and reproducible manner.

They recently reached a particularly exciting stage of the project where they will be able to take optical recordings of large sets of neural activity while mice are engaged in the task. These behavioral and neural datasets will allow them to search for the neural computations that are employed during the formation and implementation of a choice, and how these computations are disrupted when lapses in accurate decision-making take place.

Mr. Barber is hopeful that this project will expand our understanding of a fundamental cognitive process and potentially provide a new perspective on how correct and incorrect choices are formed in the brain.

A third year M.D., Ph.D. student in the Strickland laboratory. She is investigating how certain dietary fats may protect the brain from amyloid-beta buildup. Her preliminary work suggests a protective effect of a high-fat diet when fed to AD mice before onset of pathology.

Ms. Sweetland-Martin is planning additional experiments to validate whether this effect can be observed in other mouse lines, such as one with mutations affecting the amyloid precursor protein. She and her colleagues will also explore whether a high fat diet affects the vascular microenvironment in the mice brains and test various configurations of dietary fats and other compounds to determine if there is an optimal diet for neuroprotection.

A student in the  Tri-Institutional  M.D.-Ph.D.  Program,  Ms.  Sweetland-Martin  has  completed  her initial medical  training  at  Weill   Cornell  Medical  College  and  is  currently  conducting  doctoral  research at Rockefeller under the mentorship of Drs. Sidney Strickland and Erin Norris. Her Ph.D. work investigates the effects of an early lipid-rich diet on the amelioration  of  Alzheimer’s  disease pathology and cognitive decline. As a future physician-scientist, Ms. Sweetland-Martin is dedicated  to working with the geriatric population to further scientific knowledge and improve patient care and outcomes for neurodegenerative diseases. She is grateful for the opportunities provided  by  The Fisher Center for Alzheimer’s Research Foundation and is eager to continue her research career investigating Alzheimer’s Disease, dementia, and the pathology of aging.

A third year Ph.D. student in the Heintz laboratory. She is examining the molecular changes that occur in the human hippocampus during early-stage Alzheimer’s disease. The hippocampus is a region of the brain that is critical for memory and spatial cognition, and it consists of various neuronal subtypes that are differentially affected as the disease progresses. By comparing vulnerable and resistant cell types, she may be able to find molecular targets to protect neurons against Alzheimer’s pathology.

To do this, Ms. Siantoputri will isolate neuronal and glial cell types from postmortem human hippocampus tissue from donors at different stages of Alzheimer’s disease. She will use a technique called Fluorescent Activated Nuclei Sorting (FANS) followed by multi-omics sequencing to characterize each cell type throughout disease progression. Ms. Siantoputri proposes additional studies to find specific molecular targets and modulate the expression of those targets to glean information on possible mechanisms of selective vulnerability in Alzheimer’s disease.

Ms. Siantoputri spent her childhood in Indonesia before moving to Singapore at the age of 15 to further her education. Her father’s battle with neurodegenerative disease piqued an interest in the subject, leading her to shift into neuroscience research despite obtaining an undergraduate degree in biomedical engineering. When she started in the graduate program at Rockefeller, she rotated in various Alzheimer’s disease labs and became increasingly fascinated by the field. This led to her current project, studying the molecular changes that cause selective cellular vulnerability in Alzheimer’s disease. Ms. Siantoputri aspires to enhance our understanding of the disease and contribute to the ongoing search for effective therapeutic strategies. In addition to this research, she dedicates time to volunteering for outreach initiatives that aim to make science education more accessible to underrepresented communities. In her free time, she enjoys drawing, painting, and taking long walks around the city.