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Pharmaceutical Sciences Takes Center Stage for University’s CURE Scholars

Local middle school students gain hands-on experience conducting fun-filled science experiments under supervision of faculty at the School of Pharmacy.

Students from the University of Maryland, Baltimore (UMB) CURE Scholars Program visited the University of Maryland School of Pharmacy throughout the month of July to gain hands-on experience conducting research in the field of pharmaceutical sciences. The visits were organized by Lisa Jones, PhD, assistant professor in the Department of Pharmaceutical Sciences (PSC) at the School of Pharmacy, as part of her $1.1 million CAREER Award from the National Science Foundation, which supports her ongoing work to develop a new method to study the structure of cell membrane proteins in the cellular environment.

“One of the key components of the CAREER Award is that the awardee not only conducts his or her own research, but also creates an education plan aimed at fostering the development of young researchers,” says Jones. “I was thrilled to have an opportunity to collaborate with the UMB CURE Scholars Program for my education plan, and offer local middle school students a chance to conduct hands-on research in a laboratory setting at the School. I hope their time with us helped them uncover a love of science as well as a desire to pursue a career in science, technology, engineering, or math (STEM).”

Training the Next Generation of STEM Leaders

Established in 2015, the UMB CURE Scholars Program prepares middle and high school students in Baltimore for competitive, lucrative, and rewarding research and health care careers at UMB and other health institutions in the region. The program is a partnership with three public schools in West Baltimore – Franklin Square Elementary and Middle School, Green Street Academy, and Southwest Baltimore Charter School – that provides career navigation, workforce training, and mentorship to underrepresented scholars at all stages or academic and career development.

More than 20 middle school students participating in the UMB CURE Scholars Programs visited the School of Pharmacy on July 6-7 and July 13-14, where they attended brief lectures and participated in hands-on experiments related to the lecture topics in one of the School’s state-of-the-art laboratories. Topics covered during the lectures included the role of DNA in cancer, the incidence of obesity in the United States, recombinant DNA technology, and protein-based drugs. In the lab, students had an opportunity to extract DNA from strawberries and kiwis, test calories in foods such as marshmallows and popcorn, and express and purify a protein in E. coli.

“Studies have indicated that middle school is the best time to capture students’ interest in STEM,” says Jones. “However, you will be hard-pressed to capture much interest by sitting students at a desk all day. The hands-on experiments that students conducted in our lab not only reinforced lessons from our lectures, but were also fun and gave them opportunities to engage with the material and learn from each other – opportunities that they might not have in a typical middle school science classroom.”

Bringing Lessons Learned Home

Students visiting the School on July 7 also had a chance to participate in a special activity hosted by Sarah Michel, PhD, professor in PSC. Inspired by the water crisis in Flint, Mich., Michel asked students to bring a sample of tap water from their homes to test for metal ions using inductively coupled plasma mass spectrometry (ICP-MS) – the same method used by researchers who tested the water in Flint – in the School’s Mass Spectrometry Center. With assistance from a postdoctoral fellow and two summer interns in Michel’s laboratory, the students tested and analyzed the levels of toxic metals such as lead and cadmium, as well as non-toxic metals such as iron, zinc, and copper, in their water samples.

“Most individuals likely assume that drinking water in the U.S. is safe regardless of where one lives,” says Michel. “The Flint water crisis was an eye-opening experience for many of us, but I hope that it can serve as an example to these students of how science can help solve real life problems. The scientists who brought to light the drinking water crisis in Flint used their expertise in analytical chemistry to help uncover the lead contamination in the water and, as a result, the city, state, and country took notice. Scientists helped solve this big problem, and I want to inspire the CURE scholars to pursue science and solve other big problems.”

After speaking with students in the program, it appears that both Jones and Michel’s messages are resonating.

“Before I joined the UMB CURE Scholars Program, I thought science was mostly about reading books,” says Tyler McKinsey, a soon-to-be eighth grader at Green Street Academy. “Now, I understand that there are a lot of opportunities for me in science. I like working with my partners on the different projects and knowing that, if my ideas aren’t working, they will have other ideas that we can test, since we’re all contributing to the same project. I’m also looking forward to becoming a surgeon.”

  
Malissa Carroll Community Service, Education, UMB NewsJuly 28, 20170 comments
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Stroke Study

Study Links Gene Mutation to Increased Risk for Stroke

Patrick Wintrode, PhD, associate professor in the Department of Pharmaceutical Sciences (PSC) at the University of Maryland School of Pharmacy, recently collaborated on a large, multinational study that linked a single amino acid variant in the protein coding gene SERPINA1 to an increased risk for large artery stroke. Published in Proceedings of the National Academy of Sciences (PNAS), the study leveraged Wintrode’s expertise in hydrogen-deuterium exchange mass spectrometry to characterize the amino acid substitution, which occurs in the protein alpha-1 antitrypsin (AAT) and was previously believed to be a “silent” mutation with no association to any disease in the body.

“Previous research has shown that stroke, particularly the atherosclerotic form large artery stroke, is a highly heritable condition,” says Rainer Malik, PhD, postdoctoral researcher at the Institute for Stroke and Dementia Research at Klinikum der Universität München in Munich, Germany and lead author of the study. “However, the mechanisms surrounding how an individual’s risk for stroke is passed down from generation to generation remain unclear. The goal of this study was to identify new genes that could potentially indicate whether an individual is at an increased risk for suffering a large artery stroke during his or her lifetime.”

Inheriting Risk

According to the study published by Malik and his colleagues, stroke is the leading cause of long-term disability and the second most common cause of death worldwide. The American Stroke Association reports that large artery strokes occur when a large artery feeding the brain becomes blocked. These blockages often occur as a result of atherosclerosis (hardening and narrowing of the arteries), when the plaques that contribute to the hardening and narrowing of the arteries rupture and break off to travel to another part of the body – in this instance, the brain. Malik and his colleagues note that large artery strokes exhibit the highest heritability of all stroke subtypes, with an estimated 40 to 66 percent of individuals inheriting their risk for stroke from their parents.

For this study, researchers used an innovative exome chip strategy to compare the genomes of 3,127 patients from across Europe, Australia, and South Asia who suffered a large artery stroke with the genomes of 9,778 disease-free patients. The team found two genome-wide variants: one in the gene HDAC9, an already established risk factor for large artery stroke, and another in SERPINA1. A closer inspection of SERPINA1 revealed that a single amino acid substitution in AAT placed individuals at an increased risk for experiencing a large artery stroke. Following this discovery, Malik reached out to Wintrode for assistance characterizing the substitution using hydrogen-deuterium exchange mass spectrometry.

“Although the mutation was clearly associated with an increased risk for large artery stroke, it did not appear to result in significantly impaired function or protein misfolding,” says Wintrode, whose previous research has examined AAT deficiency and been supported by organizations such as the Alpha-1 Foundation, which provides support for AAT-deficient patients. “Because my team at the School of Pharmacy has published numerous studies on AAT and other proteins in the same family, Dr. Malik and his colleagues reached out to us for assistance with comparing the mutation’s properties to the more common variant.”

Solving a Mystery With Mass Spectrometry

At the School of Pharmacy, Wintrode’s research – which he often conducts using the cutting-edge equipment in the School’s Mass Spectrometry Center – focuses on protein folding and misfolding, as well as the role of protein dynamics in function and allosteric regulation. Although the mutated AAT displayed no structural abnormalities, Wintrode and his team – Daniel Deredge, PhD, postdoctoral fellow in PSC, and Anirudh Sivakumar, undergraduate summer research intern in PSC – found that it caused portions of the protein to become less stable. He notes that the increased structural fluctuations associated with the mutated AAT might interfere with the protein’s ability to interact with other proteins.

“Other proteins in the same family as AAT are often recruited to specific locations, such as clots or plaques, through interactions with other proteins or carbohydrates,” says Wintrode. “Concentrating these proteins at these locations enhances their function. However, in addition to being more flexible, the AAT mutation identified in this study interacts more weakly with lipoproteins than the more common variant of this gene. This could result in less AAT being concentrated at atherosclerotic plaques.”

Malik and his colleagues agree that the findings from this study emphasize the importance of every amino acid change that occurs in the body, noting that even those substitutions that do not directly influence a protein’s function can still affect the way in which those proteins interact with and bind to other molecules.

“One of the most interesting aspects of our research is that the amino acid substitution we identified commonly occurs in humans, but has never before been associated with disease,” says Malik. “We are excited to take our findings to the next level and further explore the role of AAT and AAT-neutrophil elastase (NE) complexes in the development and progression of atherosclerosis. In the future, it is our hope that drugs designed to treat patients with AAT deficiency might also be beneficial to patients who have been diagnosed with other conditions in which AAT has been shown to play an important role, including large artery stroke.”

  
Malissa Carroll ABAE, Collaboration, Education, People, Research, UMB NewsApril 3, 20170 comments
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Mass Spectrometry

Mass Spectrometry Center Using iLab Solutions

The University of Maryland School of Pharmacy Mass Spectrometry Center is excited to now be using iLab Solutions, an online system to streamline the process of ordering and billing for core service requests. All facility users are invited to use the system, which requires a one-time registration as discussed below. Once you are registered, the system will enable you to place service requests, provide required approvals, and monitor progress.

To get started, you must register for an account:

  1. Navigate to the core page here: Mass Spec. iLab Page
  2. If you are not a UMB user, click “sign-up” and follow the on-screen prompts
  3. If you are a UMB user, click the green “Log in” button
    • Under UMB user, click “here” to be redirected to the authentication page
    • Once you have entered your credentials, click the “Log in” button
    • You will be directed to an iLab Registration page where you will need to select your PI/Lab, and verify your contact information
    • Once your registration has been submitted, your PI will receive a notification that you have requested membership to their lab in iLab. They will need to approve your membership and assign a project number for your use.

Create a Service Request

  1. Using your iLab/UMB login credentials, log in at the core page here: Mass Spec. iLab Page
  2. Select the “Request Services” tab and click on the “Request Service” button next to the service of interest
  3. You will be asked to complete a form before submitting the request to the core
  4. Your request will be pending review by the core. The core will review your request and either agree to the work or they will ask for more information, if needed.

Create an Equipment Reservation

  1. Using your iLab/UMB login credentials, log in at the core page here: Mass Spec. iLab Page
  2. Select the “Schedule Equipment” tab and click on the “View Schedule” button next to the instrument of interest. Click and drag the time frame for which you would like to schedule your reservation.
  3. A window will pop up that will allow you to verify your reservation details and provide payment information before saving the reservation.

Additional Help

More detailed instructions are available in the customer manual. For any questions not addressed in the manual, click on the “leave iLab feedback” link in the upper right-hand corner, or contact support@ilabsolutions.com.

  
Jeremy DoggettABAE, Bulletin Board, Collaboration, Education, People, Research, TechnologyApril 20, 20160 comments
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Pharmacy’s Kane to Test New Biomarkers of Fetal Alcohol Spectrum Disorders

Maureen Kane, PhD, assistant professor in the Department of Pharmaceutical Sciences (PSC) at the School of Pharmacy and co-director of the School’s Mass Spectrometry Center, has received a three-year, $75,849 National Institutes of Health (NIH)/National Institute on Alcohol Abuse and Alcoholism (NIAAA) R15 grant subaward from the University of New Mexico College of Pharmacy to use mass spectrometry to evaluate and measure the presence of biomarkers for exposure to alcohol during pregnancy in meconium – an infant’s first stool.

Her findings will determine if the biomarkers can reliably identify infants who were prenatally exposed to alcohol, as well as help other researchers determine how exposure to alcohol interacts with exposure to environmental heavy metals found in mine wastes to affect birth outcomes and development in children during the first year of life.

Increasing Opportunities to Collaborate

“This project is an excellent example of how the tools and expertise available through the School’s Mass Spectrometry Center have increased our opportunities to collaborate with researchers across the University of Maryland, Baltimore (UMB) and beyond,” says Kane. “Research that examines how prenatal alcohol exposure interacts with exposure to other environmental toxicants is limited. Using the Mass Spectrometry Center’s state-of-the-art instrumentation, we aim to quantify reliable biomarkers that will better detect an infant’s risk for neurodevelopmental delays among newborns who were not only affected by prenatal exposure to alcohol, but to other toxic substances in the environment as well.”

About the Study

For the study – “Interactive Effect of Environmental Exposures and Alcohol in the Navajo Birth Cohort” – Kane will use mass spectrometry to measure the presence of three biomarkers – any biological molecule found in an individual’s blood or bodily fluids and tissues that indicates the presence of disease, infection, or environmental exposure – in the meconium of more than 300 newborns from the Navajo Nation: fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), and ethyl sulfate (EtS).

Meconium, which consists of substances ingested while an infant was in utero, is routinely used in newborn screenings to determine whether he or she was exposed to illicit drugs. The study will be led by co-principal investigators Johnnye Lewis, PhD, professor in the Department of Pharmaceutical Sciences at the University of New Mexico College of Pharmacy and director of the Community Environmental Health Program, and Ludmila Bakhireva, MD, PhD, MPH, associate professor in the Department of Pharmacy Practice at the College of Pharmacy. The meconium samples will come from Lewis’s Navajo Birth Cohort Study.

A Unique Partnership Between Schools

“Because the consumption of alcohol during pregnancy affects a number of additional outcomes that we want to measure in the Navajo Birth Cohort Study, our research team knew that it would be important to support a project that would produce an independent measure of alcohol consumption,” says Lewis. “Dr. Kane’s knowledge of mass spectrometry and previous experience with biomarkers of prenatal exposure to alcohol will not only contribute to the goals of our project, but will also allow our team develop a control for co-exposures to help determine whether any interactions exist between alcohols and metals exposure.”

Improving Reproductive Health Outcomes

“This project represents a unique partnership between two schools of pharmacy and the tribal community,” adds Bakhireva. “Dr. Kane’s expertise in mass spectrometry will be crucial in helping us to accurately assess prenatal alcohol exposure in a study population that is largely underrepresented in research. Ultimately, our goal is to reduce health disparities and improve reproductive health outcomes among Native Americans.”

There are more than 1,000 abandoned uranium mine waste sites across the Navajo Nation, and more than 10,000 in the western United States. The Navajo Birth Cohort Study was launched in response to community members and the Navajo Nation’s concerns about how exposures to these heavy metal mixtures could affect the health of their children. “If successful, our findings could lead to earlier recognition of risk, which would allow for earlier interventions that could improve developmental outcomes for those children affected by these exposures,” says Kane.

  
Malissa CarrollCollaboration, Research, Technology, UMB NewsSeptember 12, 20140 comments
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