Westmark Lab

Project Description: Our long-term goal is to implement a dietary intervention (restriction of soy-based infant formula in vulnerable populations) to reduce the incidence of childhood autism and obesity. The overall objective of this grant application is to identify nutritional biomarkers that are correlated with the consumption of a soy protein and obesity. The central hypothesis driving this proposal is that specific metabolic and proteomic biomarkers that are responsive to high dietary consumption of soy protein can be identified. Our hypothesis developed from our FRAXA Research Foundation-funded work (2008-2010) to evaluate the efficacy of the metabotropic glutamate receptor 5 (mGluR₅) antagonist fenobam in mice. During the course of this work, we incorporated fenobam into a purified ingredient diet (casein-protein based) to ensure reproducibility in the formulation. Surprisingly, we discovered that the placebo purified diet significantly reduced seizure incidence and weight gain in juvenile mice in comparison to mice maintained on a standard rodent chow (Purina 5015, soy-based). The human correlate of juvenile mice fed a single-source, soy-based rodent chow is infants fed soy-based formula. Subsequent medical record and survey analyses suggest that consumption of soy-based infant formula could be contributing to the autism and obesity epidemics. This project is a collaborative effort with Dr. Lingjun Li in the School of Pharmacy to identify and validate nutritional biomarkers associated with soy protein by mass spectrometry.

 Pamela Westmark: Pam is an Associate Scientist at the UW-Madison with extensive experience in rodent behavior, molecular biology and microscopy. She joined the laboratory in the Summer of 2018 and has spearheaded the use of sleep EEG and DEXA methodologies in the laboratory. She works closely with the students to ensure scientific rigor and reproducibility in the experiments.

Alejandra (Lexi) Gutierrez: Lexi joined the Westmark Laboratory during the summer of 2018 as part of the Molecular & Environmental Toxicology Summer Research Opportunities Program, she returned to her undergraduate institution Philander Smith College to complete her degree in Biology, and then joined the laboratory as a graduate student research assistant in the Fall of 2019. Lexi plays a vital role in the maintenance of our mouse colony, which benefits all of the research projects in the laboratory.

 Greg Lyon: Greg is a junior at the UW-Madison pursuing a major in Biology. He joined the Westmark laboratory in the Fall of 2019 as a Bio152 student and stayed for the remainder of his undergraduate career. Greg plans to matriculate into medical school in the Fall of 2023 and eventually use his research and medical school training to contribute to a cure for Ehlers Danlos syndrome. Greg conducts DEXA scanning and molecular analysis related to bone density in mice as a function of soy- and casein-based diets.

Brynne Boeck: Brynne is a sophomore at the UW-Madison majoring in Genetics and Neurobiology. She joined the Westmark laboratory in the Fall of 2021 as a Bio152 student with great enthusiasm and interest to contribute to our research program. She is studying transgenerational effects of soy- and casein-based diets in the mice as well as the effects of individual diet components.

Project Description: Fragile X syndrome is a rare disorder characterized by intellectual disability and a high seizure rate. Our research examines pharmaceutical and dietary approaches that reduce seizures in fragile X syndrome. The audiogenic seizure testing we perform is a routine test to assess seizure threshold, but there are only a handful of academic laboratories that are skilled in the methodology. The testing is beneficial to the pharmaceutical industry because positive results promote repurposing of their drugs to treat rare disorders. The testing is beneficial to families with Fragile X in that results provide preclinical efficacy data for novel treatments and identify candidate compounds to move on to clinical trials. This study is a continuation of a multi-part project intended to examine the efficacy of novel Angelini Pharma compounds in a mouse model of fragile X syndrome (Fmr1^KO mice). This phase of the project will test new Angelini Pharma compound(s) in Fmr1^KO mice in comparison to controls in the audiogenic seizure assay.

Pamela Westmark: Pam is an Associate Scientist at the UW-Madison with extensive experience in rodent behavior, molecular biology and microscopy. She joined the laboratory in the Summer of 2018 and has spearheaded the use of sleep EEG and DEXA methodologies in the laboratory. She works closely with the students to ensure scientific rigor and reproducibility in the experiments.

 Nathan Ripp: Nate is a junior at the UW-Madison majoring in Neurobiology. He joined the Westmark laboratory in the Fall of 2021 with a strong interest in Alzheimer’s disease and seizures. His career goal is to attend medical school and become a Doctor of Osteopathic Medicine. He is performing drug dosing and seizure testing in the mice.

Project Description: The ketogenic diet is highly effective at attenuating seizures in refractory epilepsy, and accumulating evidence in the literature suggests that it may be beneficial in treating autism. To our knowledge, no one has studied ketogenic, Atkins or other high fat/low carbohydrate diets in any model of fragile X syndrome (FXS). We tested the effects of chronic ketogenic diet treatment on seizures, body weight, ketone and glucose levels, diurnal activity levels, learning and memory, and anxiety behaviors in Fmr1^KO and littermate control mice as a function of age (Westmark et al, 2020). The ketogenic diet selectively attenuates seizures in male but not female Fmr1^KO mice and differentially affects weight gain and diurnal activity levels dependent on Fmr1 genotype, sex and age. Our FRAXA Fellowship grant will test less stringent high fat/low carbohydrate diets. Specific Aims include: (1) screen dietary percent fat and carbohydrate content for efficacy in attenuating audiogenic-induced seizures (AGS) in Fmr1^KO mice; (2) test high fat/low carbohydrate diets on circadian activity levels in Fmr1^KO mice; and (3) develop a cell culture model to screen the effects of diet on neuronal cells, for example, testing the effects of varied dietary components including ketones and ketogenic amino acids on mouse primary Fmr1^KO neuronal cell phenotypes (viability, growth, mitochondrial function).

Alejandra (Lexi) Gutierrez): Lexi joined the Westmark Laboratory during the summer of 2018 as part of the Molecular & Environmental Toxicology Summer Research Opportunities Program, she returned to her undergraduate institution Philander Smith College to complete her degree in Biology, and then joined the laboratory as a graduate student research assistant in the Fall of 2019. Lexi plays a vital role in the maintenance of our mouse colony, which benefits all of the research projects in the laboratory. We were recently awarded a FRAXA Research Fellowship so that she can study the effects of modified ketogenic diets on behavior and molecular phenotypes in Fmr1KO mice.