Fluoride anions (F-) are ubiquitous in the environment. Membrane-permeable HF (pKa=3.4) in the environment (~5.5 pH) diffuses into the cytoplasm (~7 pH) under acidic conditions where it then dissociates into F- at neutral pH, leading to an accumulation of F-. This phenomenon is called the weak acid accumulation effect. To combat this effect, microorganisms use F- exporters like Fluc to maintain levels below inhibitory concentrations. Two important features of Fluc channels differentiate them from other ion channels. 1)Fluc channels are unusually specific for F- over Cl- and 2)its dual-topology dimeric architecture, which is formed by the assembly of two polypeptides in an antiparallel transmembrane orientation.
During the pandemic, I worked on solving an x-ray crystal structure of a Fluc channel. I used data collected by Stockbridge Lab postdoctoral fellow Dr. Ben McIlwain. My thesis will also involve a structural analysis of the channels.
I plan to use electrophysiology to gain a better understanding of how bacteria transport charged substrates to modulate membrane potential. I will use electrophysiology to understand how ion channels distinguish between F- and chloride ions. I will use mutagenesis to identify mutants that reduce selectivity. Since Fluc channels are so selective for F-, Fluc channels are good model systems for understanding anion selectivity by ion channels.
I co-founded the Flint Justice Partnership (FJP) to promote awareness about the ongoing Flint water crisis. Since its inception, our organization has grown to 35 members, developed a partnership with the Center for Social Solutions at the University of Michigan, and received $6000 in grants.
On campus, we facilitate dialogues and speaker events about the crisis to raise awareness among students. In Flint, we coordinate partnerships with over 20 organizations and volunteer on an existing project begun six years ago to provide water filter education and deliver water filters, bottled water, and food to 500+ homebound residents in the most underserved areas of Flint.
During the COVID-19 pandemic, we developed a resource page for residents in Flint. We collaborated with over 100 organizations to get accurate information and learn about the community’s needs. We have continued to run our resource page and communicate with our community partners monthly.
- Effect of KLF13 and 9 on the regulation of cell cycle and apoptotic genes
I received a research scholarship from the Molecular, Cellular, and Developmental Biology (MCDB) Department at the University of Michigan to conduct research on Krüppel-like factors (Klfs), which are a family of 17 zinc finger transcription factors. They are grouped into three subfamilies based on the sequences of their N-terminal domains, which comprise sites for interaction with coregulators. Klfs of subfamily 3 can act as transcriptional activators or repressors depending on the cellular context.
It is well known that KLF9 has important functions in the postnatal development of the central nervous system, it promotes and maintains the differentiated state of neurons, and is thus implicated in the loss of regenerative capacity of adult mammalian neurons. KLF13, similar to KLF9, inhibits the neurite outgrowth of the adult mouse hippocampus-derived cell line HT22 and axons of hippocampal neurons in primary cultures. It was recently discovered that KLF 9 and 13 down-regulate the cAMP pathway, important in regenerative responses of neurons to injury. We found that KLF 9 could block neurite outgrowth induced by the cAMP pathway.
The objective of the project was to discover the mechanism of how KLF 9 and 13 block the cAMP pathway. We investigated the regulation of Calm3, Prkaca, and Rap1a promoters by KLF 9 and 13.
- Production of a new series of ligands with potential to act as water remediators
In this Flint water crisis-inspired and green chemistry research project, a group of high schoolers, including me, created a molecule that binds to other molecules, called a ligand, capable of removing harmful substances from tainted water. We worked with Mark Benvenuto, Ph.D. at the University of Detroit Mercy to uphold the principles of green chemistry by creating a ligand that is cheap, easy-to-use, and environmentally friendly. Our goal was to positively impact Michiganders affected by the Flint water crisis.
Our research showed that if our ligand could pull metal ions into a nonpolar solution called monoglyme, it should be able to pull metal ions out of aqueous solution.
I received the 2017 American Chemical Society Ciba Travel Grant in Green Chemistry as the first high schooler recipient. This grant covered the costs for me to attend the American Chemical Society National Meeting in Boston, Massachusetts. My abstract was accepted into the Sci-Mix and Division of Environmental Chemistry poster sessions of the national conference, with the Sci-Mix poster session consisting of abstracts selected by division program chairs and representing the most exceptional abstracts submitted to participating divisions.
Our research was published in Physical Sciences Reviews.
Additional information: My group and I also presented at the ACS Central Regional Conference in Dearborn, Michigan as the only high school group there. Click here to view our abstract from the conference.
- Controlling gene expression in an in-vivo model organism
I received a full-tuition scholarship and conducted extensive, ten-day, graduate-level developmental neuroscience research with a group of high schoolers. I collaborated with the scientific community, including predecessors in the program, to present research and publish data. We conducted our research at Coastal Marine Biolabs through the NeuroLab Program, which is funded by the National Institutes of Health, and we were supervised by Ralph Imondi, Ph.D. and Linda Santschi, Ph.D.
- Role of the microRNA-183/96/182 cluster in pseudomonas aeruginosa-induced keratitis
I cold-called over 100 professors about research positions that interested me and I chose to work alongside Shunbin Xu, M.D., Ph.D. at the Wayne State University School of Medicine to conduct immunology-focused research. microRNA is a newly acknowledged level of gene expression regulation and bacterial keratitis is a corneal infection caused by bacteria commonly affecting contact-lens wearers. We specifically examined pseudomonas aeruginosa-induced keratitis, which causes blindness and visual disabilities.
We focused on the role of the microRNA-183/96/182 cluster and the ways in which it helps regulate the innate immune response to pseudomonas aeruginosa-induced keratitis infection. We also examined the potential of the anti-microRNAs, which are found in the cluster knockdown, to shield the cornea from unfavorable effects of the disease. Our research is aimed to identify new treatment strategies and therapeutic targets for the disease and other antibiotic-resistant bacterial infections and tumors that bypass the immune system.
Publications
- McIlwain, B. C., Ruprecht, M. T., & Stockbridge, R. B. (2021). Membrane Exporters of Fluoride Ion. Annual Review of Biochemistry, 90. doi: 10.1146/annurev-biochem-071520-112507.
- Pothoof, J., Ruprecht, M. T., Sliwinski, B. D., Sosnowski, B. M., Fitzgerald, P. R., Kosmas, S., & Benvenuto, M. A. (2018). Synthesis of “three-legged” tri-dentate podand ligands incorporating long-chain aliphatic moieties, for water remediators, and for isolating metal ions in non-aqueous solution. Physical Sciences Reviews, 3(11). doi: 10.1515/psr-2018-0076.
Media
- Sincerely, Hueman Podcast
- "A Campus Without Students"
- "Meet the 18-year-old tackling the Flint Water Crisis — with science"
- "Down to a science"
- "North student takes research to next level"
- "Grosse Pointe North student conducts Flint water crisis research in chemistry class"
- "Teen discovers possible fix to Flint water crisis"
- "Senior wins the American Chemistry Society Ciba Travel Award"
- "Chemistry Club research to be published"
- "Freshman capitalizes on traveling lifestyle"
On campus, we facilitate dialogues and speaker events about the crisis to raise awareness among students. In Flint, we coordinate partnerships with over 20 organizations and volunteer on an existing project begun six years ago to provide water filter education and deliver water filters, bottled water, and food to 500+ homebound residents in the most underserved areas of Flint.
During the COVID-19 pandemic, we developed a resource page for residents in Flint. We collaborated with over 100 organizations to get accurate information and learn about the community’s needs. We have continued to run our resource page and communicate with our community partners monthly.
I received a research scholarship from the Molecular, Cellular, and Developmental Biology (MCDB) Department at the University of Michigan to conduct research on Krüppel-like factors (Klfs), which are a family of 17 zinc finger transcription factors. They are grouped into three subfamilies based on the sequences of their N-terminal domains, which comprise sites for interaction with coregulators. Klfs of subfamily 3 can act as transcriptional activators or repressors depending on the cellular context.
It is well known that KLF9 has important functions in the postnatal development of the central nervous system, it promotes and maintains the differentiated state of neurons, and is thus implicated in the loss of regenerative capacity of adult mammalian neurons. KLF13, similar to KLF9, inhibits the neurite outgrowth of the adult mouse hippocampus-derived cell line HT22 and axons of hippocampal neurons in primary cultures. It was recently discovered that KLF 9 and 13 down-regulate the cAMP pathway, important in regenerative responses of neurons to injury. We found that KLF 9 could block neurite outgrowth induced by the cAMP pathway.
The objective of the project was to discover the mechanism of how KLF 9 and 13 block the cAMP pathway. We investigated the regulation of Calm3, Prkaca, and Rap1a promoters by KLF 9 and 13.
- Production of a new series of ligands with potential to act as water remediators
In this Flint water crisis-inspired and green chemistry research project, a group of high schoolers, including me, created a molecule that binds to other molecules, called a ligand, capable of removing harmful substances from tainted water. We worked with Mark Benvenuto, Ph.D. at the University of Detroit Mercy to uphold the principles of green chemistry by creating a ligand that is cheap, easy-to-use, and environmentally friendly. Our goal was to positively impact Michiganders affected by the Flint water crisis.
Our research showed that if our ligand could pull metal ions into a nonpolar solution called monoglyme, it should be able to pull metal ions out of aqueous solution.
I received the 2017 American Chemical Society Ciba Travel Grant in Green Chemistry as the first high schooler recipient. This grant covered the costs for me to attend the American Chemical Society National Meeting in Boston, Massachusetts. My abstract was accepted into the Sci-Mix and Division of Environmental Chemistry poster sessions of the national conference, with the Sci-Mix poster session consisting of abstracts selected by division program chairs and representing the most exceptional abstracts submitted to participating divisions.
Our research was published in Physical Sciences Reviews.
Additional information: My group and I also presented at the ACS Central Regional Conference in Dearborn, Michigan as the only high school group there. Click here to view our abstract from the conference.
- Controlling gene expression in an in-vivo model organism
I received a full-tuition scholarship and conducted extensive, ten-day, graduate-level developmental neuroscience research with a group of high schoolers. I collaborated with the scientific community, including predecessors in the program, to present research and publish data. We conducted our research at Coastal Marine Biolabs through the NeuroLab Program, which is funded by the National Institutes of Health, and we were supervised by Ralph Imondi, Ph.D. and Linda Santschi, Ph.D.
- Role of the microRNA-183/96/182 cluster in pseudomonas aeruginosa-induced keratitis
I cold-called over 100 professors about research positions that interested me and I chose to work alongside Shunbin Xu, M.D., Ph.D. at the Wayne State University School of Medicine to conduct immunology-focused research. microRNA is a newly acknowledged level of gene expression regulation and bacterial keratitis is a corneal infection caused by bacteria commonly affecting contact-lens wearers. We specifically examined pseudomonas aeruginosa-induced keratitis, which causes blindness and visual disabilities.
We focused on the role of the microRNA-183/96/182 cluster and the ways in which it helps regulate the innate immune response to pseudomonas aeruginosa-induced keratitis infection. We also examined the potential of the anti-microRNAs, which are found in the cluster knockdown, to shield the cornea from unfavorable effects of the disease. Our research is aimed to identify new treatment strategies and therapeutic targets for the disease and other antibiotic-resistant bacterial infections and tumors that bypass the immune system.
Publications
- McIlwain, B. C., Ruprecht, M. T., & Stockbridge, R. B. (2021). Membrane Exporters of Fluoride Ion. Annual Review of Biochemistry, 90. doi: 10.1146/annurev-biochem-071520-112507.
- Pothoof, J., Ruprecht, M. T., Sliwinski, B. D., Sosnowski, B. M., Fitzgerald, P. R., Kosmas, S., & Benvenuto, M. A. (2018). Synthesis of “three-legged” tri-dentate podand ligands incorporating long-chain aliphatic moieties, for water remediators, and for isolating metal ions in non-aqueous solution. Physical Sciences Reviews, 3(11). doi: 10.1515/psr-2018-0076.
Media
- Sincerely, Hueman Podcast
- "A Campus Without Students"
- "Meet the 18-year-old tackling the Flint Water Crisis — with science"
- "Down to a science"
- "North student takes research to next level"
- "Grosse Pointe North student conducts Flint water crisis research in chemistry class"
- "Teen discovers possible fix to Flint water crisis"
- "Senior wins the American Chemistry Society Ciba Travel Award"
- "Chemistry Club research to be published"
- "Freshman capitalizes on traveling lifestyle"
It is well known that KLF9 has important functions in the postnatal development of the central nervous system, it promotes and maintains the differentiated state of neurons, and is thus implicated in the loss of regenerative capacity of adult mammalian neurons. KLF13, similar to KLF9, inhibits the neurite outgrowth of the adult mouse hippocampus-derived cell line HT22 and axons of hippocampal neurons in primary cultures. It was recently discovered that KLF 9 and 13 down-regulate the cAMP pathway, important in regenerative responses of neurons to injury. We found that KLF 9 could block neurite outgrowth induced by the cAMP pathway.
The objective of the project was to discover the mechanism of how KLF 9 and 13 block the cAMP pathway. We investigated the regulation of Calm3, Prkaca, and Rap1a promoters by KLF 9 and 13.
In this Flint water crisis-inspired and green chemistry research project, a group of high schoolers, including me, created a molecule that binds to other molecules, called a ligand, capable of removing harmful substances from tainted water. We worked with Mark Benvenuto, Ph.D. at the University of Detroit Mercy to uphold the principles of green chemistry by creating a ligand that is cheap, easy-to-use, and environmentally friendly. Our goal was to positively impact Michiganders affected by the Flint water crisis.
Our research showed that if our ligand could pull metal ions into a nonpolar solution called monoglyme, it should be able to pull metal ions out of aqueous solution.
I received the 2017 American Chemical Society Ciba Travel Grant in Green Chemistry as the first high schooler recipient. This grant covered the costs for me to attend the American Chemical Society National Meeting in Boston, Massachusetts. My abstract was accepted into the Sci-Mix and Division of Environmental Chemistry poster sessions of the national conference, with the Sci-Mix poster session consisting of abstracts selected by division program chairs and representing the most exceptional abstracts submitted to participating divisions.
Our research was published in Physical Sciences Reviews.
Additional information: My group and I also presented at the ACS Central Regional Conference in Dearborn, Michigan as the only high school group there. Click here to view our abstract from the conference.
- Controlling gene expression in an in-vivo model organism
I received a full-tuition scholarship and conducted extensive, ten-day, graduate-level developmental neuroscience research with a group of high schoolers. I collaborated with the scientific community, including predecessors in the program, to present research and publish data. We conducted our research at Coastal Marine Biolabs through the NeuroLab Program, which is funded by the National Institutes of Health, and we were supervised by Ralph Imondi, Ph.D. and Linda Santschi, Ph.D.
- Role of the microRNA-183/96/182 cluster in pseudomonas aeruginosa-induced keratitis
I cold-called over 100 professors about research positions that interested me and I chose to work alongside Shunbin Xu, M.D., Ph.D. at the Wayne State University School of Medicine to conduct immunology-focused research. microRNA is a newly acknowledged level of gene expression regulation and bacterial keratitis is a corneal infection caused by bacteria commonly affecting contact-lens wearers. We specifically examined pseudomonas aeruginosa-induced keratitis, which causes blindness and visual disabilities.
We focused on the role of the microRNA-183/96/182 cluster and the ways in which it helps regulate the innate immune response to pseudomonas aeruginosa-induced keratitis infection. We also examined the potential of the anti-microRNAs, which are found in the cluster knockdown, to shield the cornea from unfavorable effects of the disease. Our research is aimed to identify new treatment strategies and therapeutic targets for the disease and other antibiotic-resistant bacterial infections and tumors that bypass the immune system.
Publications
- McIlwain, B. C., Ruprecht, M. T., & Stockbridge, R. B. (2021). Membrane Exporters of Fluoride Ion. Annual Review of Biochemistry, 90. doi: 10.1146/annurev-biochem-071520-112507.
- Pothoof, J., Ruprecht, M. T., Sliwinski, B. D., Sosnowski, B. M., Fitzgerald, P. R., Kosmas, S., & Benvenuto, M. A. (2018). Synthesis of “three-legged” tri-dentate podand ligands incorporating long-chain aliphatic moieties, for water remediators, and for isolating metal ions in non-aqueous solution. Physical Sciences Reviews, 3(11). doi: 10.1515/psr-2018-0076.
Media
- Sincerely, Hueman Podcast
- "A Campus Without Students"
- "Meet the 18-year-old tackling the Flint Water Crisis — with science"
- "Down to a science"
- "North student takes research to next level"
- "Grosse Pointe North student conducts Flint water crisis research in chemistry class"
- "Teen discovers possible fix to Flint water crisis"
- "Senior wins the American Chemistry Society Ciba Travel Award"
- "Chemistry Club research to be published"
- "Freshman capitalizes on traveling lifestyle"
Our research showed that if our ligand could pull metal ions into a nonpolar solution called monoglyme, it should be able to pull metal ions out of aqueous solution.
I received the 2017 American Chemical Society Ciba Travel Grant in Green Chemistry as the first high schooler recipient. This grant covered the costs for me to attend the American Chemical Society National Meeting in Boston, Massachusetts. My abstract was accepted into the Sci-Mix and Division of Environmental Chemistry poster sessions of the national conference, with the Sci-Mix poster session consisting of abstracts selected by division program chairs and representing the most exceptional abstracts submitted to participating divisions.
Our research was published in Physical Sciences Reviews.
Additional information: My group and I also presented at the ACS Central Regional Conference in Dearborn, Michigan as the only high school group there. Click here to view our abstract from the conference.
I received a full-tuition scholarship and conducted extensive, ten-day, graduate-level developmental neuroscience research with a group of high schoolers. I collaborated with the scientific community, including predecessors in the program, to present research and publish data. We conducted our research at Coastal Marine Biolabs through the NeuroLab Program, which is funded by the National Institutes of Health, and we were supervised by Ralph Imondi, Ph.D. and Linda Santschi, Ph.D.
I cold-called over 100 professors about research positions that interested me and I chose to work alongside Shunbin Xu, M.D., Ph.D. at the Wayne State University School of Medicine to conduct immunology-focused research. microRNA is a newly acknowledged level of gene expression regulation and bacterial keratitis is a corneal infection caused by bacteria commonly affecting contact-lens wearers. We specifically examined pseudomonas aeruginosa-induced keratitis, which causes blindness and visual disabilities.
We focused on the role of the microRNA-183/96/182 cluster and the ways in which it helps regulate the innate immune response to pseudomonas aeruginosa-induced keratitis infection. We also examined the potential of the anti-microRNAs, which are found in the cluster knockdown, to shield the cornea from unfavorable effects of the disease. Our research is aimed to identify new treatment strategies and therapeutic targets for the disease and other antibiotic-resistant bacterial infections and tumors that bypass the immune system.
We focused on the role of the microRNA-183/96/182 cluster and the ways in which it helps regulate the innate immune response to pseudomonas aeruginosa-induced keratitis infection. We also examined the potential of the anti-microRNAs, which are found in the cluster knockdown, to shield the cornea from unfavorable effects of the disease. Our research is aimed to identify new treatment strategies and therapeutic targets for the disease and other antibiotic-resistant bacterial infections and tumors that bypass the immune system.