Student Seminars and Defenses

Adam Roszczyk & Caleb Mahlen - PhD Candidates

Titles: TBD

Faculty Evaluators: Manoela Fogaca & Andrew Wojtovich

Student Moderator: Tanique McDonald

 Apr 07, 2025 @ 4:00 p.m.
 Medical Center | K307

Dominic Bunn - PhD Candidate, Neuroscience Graduate Program

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of tau and amyloid beta aggregates, reactive astrocytes, activated microglia, and oxidative stress. Tau aggregation is considered a primary driver of the disease, with systematic propagation of tau pathology through the brain in Braak stages. Astrocytes are known to uptake tau, but whether this is beneficial or detrimental is still debated. Mitochondrial reactive oxygen species (ROS) production is one regulator of astrocyte function, as their mitochondria are known to generate an increased amount of ROS compared to other cell types. This mitochondrial ROS production is utilized for signaling that regulates many astrocytic functions. Despite oxidative stress being an early hallmark of AD that has been extensively studied, the specific relationship between astrocytic ROS and tau pathology is unknown. Interestingly, exposure to pathological tau induces mitochondrial dysfunction in astrocytes. Neonatal astrocytes from tauopathy models also adopt abnormal phenotypes, with increased reactivity markers and reduced neurosupportive functions. While no studies have looked at the impact of mitochondrial ROS on astrocytic tau uptake specifically, astrocytic upregulation of BAG3 and transcription factor EB have been shown to increase uptake and have neuroprotective effects in AD. Both proteins are suggested to be regulated by Nrf2 activity, which responds to oxidative stress. These studies suggest mitochondrial ROS is an important regulator of astrocyte function within AD, but the specific relationship has never been directly explored. We hypothesize that increased mitochondrial ROS production will increase tau uptake but impair the ability of the astrocytes to degrade uptaken tau and reduce their neuroprotective functions. To test this hypothesis, we propose to use in vitro approaches that allow for spatially and temporally controlled ROS production. We will generate ROS within the mitochondria of AD model-derived astrocytes. The AD model used is the PS19 mouse model, which expresses human tau with the P301S mutation, known to cause tau pathology in humans, under the mouse prion promoter. While significant tau aggregate pathology is not observed until 6 months in the PS19 model, the prion promoter is active shortly after neurons differentiate. In Aim 1, we will utilize chemogenetics to generate mitochondrial ROS, alongside the ROS biosensor HyPer7, to assess the impact of mitochondrial ROS production on astrocyte mitochondrial health, and neurosupportive functions. The goal of this aim is to understand basal differences in ROS production, ROS sensitivity, and mitochondrial function between PS19 and wild type astrocytes In Aim 2, we will utilize chemogenetic approaches of generating mitochondrial ROS to investigate the effect of ROS on the uptake, degradation, and propagation of tau pathology. The chemogenetic control of ROS production allows for the spatial and temporal control of ROS production independent of metabolism, allowing us to test the cause and effect relationship of ROS generation and tau processing. The experiments proposed are achievable within the lab and will advance our understanding of astrocyte function and oxidative stress in the context of AD.

 Apr 10, 2025 @ 11:00 a.m.
 Medical Center | 2-7534

Tracey Preko & Skylar DeWitt - PhD Candidates

Titles: TBD

Faculty Evaluators: Samuel Norman-Haignere & Ania Busza

Student Moderator: Amelia Hines

 Apr 14, 2025 @ 4:00 p.m.
 Medical Center | K307

Wen Li & Yunshan Cai - PhD Candidates

Titles: TBD

Faculty Evaluators: Rick Libby & Ed Brown

Student Moderator: Mariah Marrero

 Apr 21, 2025 @ 4:00 p.m.
 Medical Center | K307

Joanne Chiu & Emma Bryson - PhD Candidates

Titles: TBD

Faculty Evaluators: Jean Bidlack & David Dodell-Feder

Student Moderator: Daulton Myers

 Apr 28, 2025 @ 4:00 p.m.
 Medical Center | K307

Alesandra Martin & Emma Strawderman - PhD Candidates

Titles: TBD

Faculty Evaluators: Michael Telias & Frank Garcea

Student Moderator: Jeeyun Kim

 May 05, 2025 @ 4:00 p.m.
 Medical Center | K207

Alex Solorzano & Alexis Feidl - PhD Candidates

Titles: TBD

Faculty Evaluators: John Olschowka & Debroah Cory-Slechta

Student Moderator: Margaux Masten

 May 12, 2025 @ 4:00 p.m.
 Medical Center | K207

Catalina Guzman - PhD Candidate

Title: TBD

Faculty Evaluators: Ania Majewska & Loisa Bennetto

Student Moderator: Gavin Magill

 May 19, 2025 @ 4:00 p.m.
 Medical Center | K207