Category: Faculty news

In clearest view ever of cell membrane, VCU team finds unexpected structure and new areas for pharmaceutical research

An illustration of a cell membrane.
An illustration of a cell membrane. (Getty)

For more information, contact Greg Weatherford, VCU School of Pharmacy, at goweatherfor@vcu.edu

Working with a Nobel Prize-winning biophysicist, a team of researchers at Virginia Commonwealth University has used an innovative technique to gain the clearest view yet of a patch of cell membrane and its components, revealing unexpected structures and opening up new possibilities for pharmaceutical research.

Cell membranes are formed largely of a bimolecular sheet, a fraction of the thickness of a soap bubble, in which two layers of lipid molecules are packed with their hydrophobic tails pointing inward and their hydrophilic heads outward, exposed to water.

The internal shape and structure of this lipid bilayer have remained largely mysterious after almost a century of research. This is in large part because most methods to examine membranes use detergents, which strip away the lipids that make up much of the membranes’ structures.

In a newly published paper in Proceedings of the National Academy of Sciences of the United States of America, the team — led by Youzhong Guo, Ph.D., of the Virginia Commonwealth University School of Pharmacy — used a new detergent-free method that allowed them to examine the membrane of an E. coli cell, with lipids still in place.

‘Surprising’ structure
Where earlier models had shown a fluid, almost structureless lipid layer — one often-cited research paper compared it to different weights of olive oil poured together — the VCU-led team was startled to find a distinct hexagonal structure inside the membrane. This has led the researchers to propose that the lipid layer might act as both sensor and energy transducer within a membrane protein transporter.

“The most surprising outcome is the high order with which lipid molecules are arranged, and the idea they might even cooperate in the functional cycle of the export channel,” said Joachim Frank, Ph.D., of Columbia University, a 2017 Nobel laureate in chemistry and coauthor of the paper. “It is counterintuitive since we have learned that lipids are fluid and disordered in the membrane.”

Photo of Youzhou Guo
Guo

The researchers were able to get such a clear view because they used an innovative method to isolate and stabilize the membranes. Employing poly-styrene-maleic-acid to break cell membrane into nanoparticles that were then isolated and captured in a layer of sophisticated polymer, the researchers used the state-of-the-art cryo-electron microscope at New York Structural Biology Center (NYSBC) to get a clear look at the lipid bilayer.

“Being able to pull proteins out of cell membranes without using detergents to break up the lipid bilayers truly is a fantastic advance,” said Wayne Hendrickson, Ph.D., a university professor at Columbia, scientific director of NYSBC and coauthor of the paper.

The technique and its revelations could have significant pharmaceutical value, added VCU’s Guo. He pointed out that about half of medical drugs target the cell membrane, and proposed that improved understanding of their layers of lipids and proteins could lead to new or more-effective therapies.

The authors of the paper, “Structure and Activity of Lipid Bilayer Within a Membrane Protein Transporter,” are Weihua Qiu, Guoyan G. Xu, Yan Zhang and Youzhong Guo, of Virginia Commonwealth University, and Ziao Fu, Robert A. Grassucci, Joachim Frank and Wayne A. Hendrickson of Columbia University.

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Kelly Goode on the 1918 pandemic and its lessons for today

Kelly Goode on the 1918 pandemic and its lessons for today

Kelly Goode, Pharm.D., visits a key site in the history of the 1918 flu pandemic that killed 50 million people worldwide. Hear what she has to say about what that tragic epidemic can teach us today.

Posted by VCU School of Pharmacy on Friday, October 5, 2018

VIDEO: Kelly Goode, Pharm.D., visits the site of an emergency hospital during the 1918 influenza pandemic to discuss the flu and the importance of vaccines.

Pharmacists as part of medical team make patients healthier and reduce costs, study says

A hospital bed.
How can doctors keep patients healthier and out of the hospital? By having pharmacists on the medical team, a new study says.

By Christian Ruiz
Auxiliary Label Staff

Pharmacists working in collaboration with other health-care providers can improve the quality and cost of care for patients, according to a recent study.

A recent article in the American Journal of Health-System Pharmacy makes the case that pharmacists working as part of the primary-care team can be crucial life savers for their patients. In the case of the study, having pharmacists on the team reduced hospitalizations by 23.4 percent and reduced costs by approximately $5 million.

The study — of six hospitals from the Carilion Clinic health system in southwest Virginia in conjunction with 22 patient-centered medical homes associated with Carilion Clinic — was led by VCU School of Pharmacy’s Gary Matzke, Pharm.D.; Leticia Moczygemba, Pharm.D., Ph.D.; Karen Williams, Pharm.D.; Michael Czar, Pharm.D., Ph.D.; and William Lee. The study took place from January 2013 to June 2015. Funding sources for the study included the CMS Center for Medicare and Medicaid Innovation and the Carilion Clinic health system.

A total of 2,480 patients in the study had two or more of these seven chronic health conditions: heart failure, high blood pressure, high cholesterol, diabetes, asthma, chronic obstructive pulmonary disease (COPD) and depression. In addition, the patients were taking at least four medications and had a primary care physician in the Carilion Clinic health system.

The researchers studied the difference between collaborative care, in which pharmacists were members of the primary care team and worked closely with physicians, and “usual care,” in which pharmacists were not part of the primary care team, on the progress of their patients’ chronic health conditions and on their patients’ use of hospital resources.

The collaborative-care pharmacists called patients within 72 hours after their hospital stay to see if those patients had any medication-related problems or issues. Additionally, these pharmacists met the patients face-to-face or by phone to address patient-specific problems or concerns, which encouraged patients to self-manage their medications and health conditions.

Patients in the usual-care group did not interact with pharmacists in these ways.

Patients in the group working more closely with pharmacists showed better improvement in each of their health conditions compared to the usual-care group in terms of their diabetes, high blood pressure and high cholesterol.

In addition, the number of patients who were treated with the collaborative-care group experienced a 23.4 percent decrease in hospitalizations, from 1,675 hospitalizations before treatment by the collaborative-care group to 1,283 hospitalizations after treatment by the collaborative-care group.

The usual-care group, in comparison, experienced an 8.7 percent decrease in hospitalizations, from 355 hospitalizations before treatment and 324 hospitalizations after treatment.

Along with the health improvements, pharmacists in the collaborative-care group helped reduce the cost of hospitalizations overall by $5,156,675 — $2,619 less per patient than standard procedures would have been expected to cost. In comparison, the usual-care group recorded a cost reduction of $475,071, or $241 less per patient than standard procedures would have been expected to cost. This means that pharmacists in the collaborative-care group helped save $4,681,604 more than the usual-care group — or $2,378 more per patient than standard procedures would have been expected to cost — over the course of the study.

This study demonstrates that pharmacists can contribute far more to health care in the community than just serving as “pill counters” – a perceived role that immensely underestimates and undervalues the impact they can have on both the health of their patients and the cost of health care. Additionally, when health care providers work together as a team, our jobs as life savers can be worth so much more to our patients.

Auxiliary Label is a student-created blog examining pharmacy life, education and research at the VCU School of Pharmacy from a student perspective. It is overseen by Greg Weatherford, the school’s director of communications. Contact him here.

Healthcare policy fellow to work in office of U.S. Senator Sherrod Brown

Photo of the U S Capitol
VCU School of Pharmacy alumna Tina Chhabra will spend a year working in Congress. (Photo credit)
By Greg Weatherford
Director of Communications, VCU School of Pharmacy

ACCP-ASHP-VCU Healthcare Policy Fellow Tina Chhabra has begun her congressional placement within the office of Senator Sherrod Brown of Ohio.

In her work with the office, which will run through August 2019, Chhabra (VCU Pharm.D. ‘16)  will support Senator Brown’s health team in all healthcare-related matters such as Medicare, Medicaid, drug development, mental health, the opioid crisis, the Affordable Care Act, and more.

Pharmacists selected as American College of Clinical Pharmacy-American Society of Health-System Pharmacists-Virginia Commonwealth University Congressional Healthcare Policy Fellows have the opportunity to gain real-world insight into health care policy analysis and development via immersion in the congressional environment. Fellows are actively mentored in legislative evaluation, policy development, research and writing while integrating practical experience with theory.

“There is no typical day,” Chhabra said of her role in Congress so far. Her work includes writing policy memos, participating in health-care briefings and meeting with constituents. “Constituents are the best educators,” Chhabra added. “I really enjoy meeting with the people of Ohio and learning from their experiences and expertise.”

Prior to her placement with Senator Brown’s office, and as part of the fellowship, Chhabra spent one week at the Brookings Institution and three weeks each with ACCP’s and ASHP’s government affairs offices.

The fellowship program, now directed by VCU School of Pharmacy associate professor Kristin Zimmerman, Pharm.D., was founded in 2007 under the leadership of professor Gary R. Matzke, Pharm.D.

For more about the ACCP-ASHP-VCU Congressional Healthcare Policy Fellow program, click here or contact director Kristin Zimmerman at kzimmerman@vcu.edu.

VCU School of Pharmacy is ranked among the top 20 graduate programs in pharmacy in the United States by U.S. News & World Report.

VCU Pharmacy’s CPPI announces partnership with journal Pharmacy Practice

FOR IMMEDIATE RELEASE
CONTACT: Greg Weatherford
goweatherfor@vcu.edu | (804) 828-6470 (o) (804) 937-4722 (m)

The VCU School of Pharmacy’s Center for Pharmacy Practice Innovation is proud to announce an editorial partnership with Pharmacy Practicea quarterly full-text peer-reviewed online journal.

Pharmacy Practice was founded as an independent journal by a group of prominent pharmacy-practice researchers from around the world about 10 years ago. Pharmacy Practice is free to access, complying with the NIH’s policy on public access, and does not charge for submissions or publication. It is indexed and abstracted on PubMed, PubMed Central, Embase, Scopus, Ebsco EJS and the Directory of Open Access Journals, among others.

As part of the agreement, faculty members of the VCU Center for Pharmacy Practice Innovation will have a designated section to publish non-peer-reviewed articles expressing viewpoints on a wide range of pharmacy-practice topics. VCU School of Pharmacy faculty members Teresa Salgado, M.Pharm., Ph.D. and David Holdford, Ph.D. were named associate editors of Pharmacy Practice; faculty members John Bucheit, Pharm.D.Lauren Pamulapati, Pharm.D., and Julie Patterson, Pharm.D., Ph.D. were named advisory board members.

Notably, the agreement between the journal and the center stipulates that the arrangement remains valid only as long as Pharmacy Practice does not charge authors to publish. No financial support was given or received by the VCU center to execute or maintain the agreement.

“One of our driving motivations for this partnership is to support the open-science philosophy, particularly in an area like pharmacy practice research in which many open access journals charge fees,” explained Salgado, assistant director of the VCU Center for Pharmacy Practice Innovation. “We are honored to join the prestigious group of international colleagues who are part of Pharmacy Practice’s editorial and advisory boards.”

Pharmacy Practice is ranked among the best journals in pharmacy and is among the top journals in the field as determined by the Scopus CiteScore. In fact, Pharmacy Practice is the first open-access journal in this rank.

“We are excited to have an editorial partner as esteemed as the VCU School of Pharmacy’s Center for Pharmacy Practice Innovation,” said Fernando Fernandez-Llimos, Ph.D., editor-in-chief of Pharmacy Practice. “We share the goal of supporting true open-access research of the highest caliber. We look forward to a rewarding partnership.”

For more information contact Greg Weatherford, VCU School of Pharmacy director of communications, at goweatherfor@vcu.edu.

Patricia Slattum’s 10 lessons for young pharmacists

At her keynote speech at the White Coat Ceremony for the Class of 2022, Patricia Slattum, Pharm.D., the 2018 Preceptor of the Year, offered 10 lessons drawn from her 35-year career in pharmacy:

  1. Patients always come first.
  2. There is always room for improvement!
  3. Learn to listen.
  4. Watch for assumptions — your own, and others’.
  5. Collaboration is key.
  6. Don’t be afraid to dive in.
  7. Be willing to invest in others. It pays off.
  8. Play to strengths — your own as well as your patients’ and colleagues’: “Focus on what people have, not what they don’t.”
  9. Carers must practice self-care.
  10. Pharmacy is a small world. This means that doing the right thing can be hard sometimes, but do it anyway.

Xu wins Ralph E. Powe Award from Oak Ridge Associated Universities

Qingguo Xu, assistant professor in the Department of Pharmaceutics, holds his award. He is accompanied by John Ryan, VCU associate vice president for research development, and the School of Pharmacy’s Aron Lichtman, associate dean, and Dean Joseph DiPiro.

Qingguo Xu, an assistant professor in the Department of Pharmaceutics, has received the Ralph E. Powe Award from Oak Ridge Associated Universities to support research by junior faculty.

The annual Ralph E. Powe Junior Faculty Enhancement Awards provide seed money for research by junior faculty at ORAU member institutions. These awards are intended to enrich the research and professional growth of young faculty and result in new funding opportunities, according to the organization.

VCU last received a Powe award in 2012.

Oak Ridge Associated Universities is a consortium of Ph.D.-granting institutions based in Tennessee and affiliated with the Oak Ridge National Labs, the largest science and energy laboratory in the United States, and the Oak Ridge Institute for Science and Education, supported by the U.S. Department of Energy.

Learn more about the Powe award here.

Since ancient Greece, doctors have relied on patients to tell them what medications they are taking. They may no longer need to.

 

BY GREG WEATHERFORD

Director of Communications, VCU School of Pharmacy

Every day, in thousands of emergency rooms around the world, doctors face a daunting mystery: What medications are in a patient’s body?

That question can be one of life or death, and since the days of Hippocrates doctors have relied on the same method for answers: They ask the patient.

Now, thanks to collaborative research at Virginia Commonwealth University, they may soon have a much better option.

The presence of drugs such as blood thinners or heart medications can dramatically affect the way a patient reacts to wounds or medical treatment. Unplanned withdrawal from medication can lead to medical crises in patients who are hospitalized. Drugs used in emergencies could interact badly with those that are already in a patient’s system.

“In emergencies, we have to depend on the patients or their families to tell us what they are taking,” said Sudha Jayaraman, M.D., a VCU Health surgeon who specializes in trauma and other emergency cases.

There are major drawbacks with that approach, particularly in emergencies. Patients may be unconscious or incoherent or simply unsure. Family members may not know what medicines have been prescribed, much less taken. The patients’ doctors and pharmacists may be hard to reach on short notice.

And while paramedics transporting patients to the hospital are trained to “grab all the meds and bring them in a bag,” Jayaraman said, that information is of limited use if there is no way to know which of those drugs might be in a patient’s system.

A national problem

More than half of hospitalized patients have at least one unintended drug interaction while under medical care, according to the U.S. Department of Health and Human Services. Of the unintended interactions, 39 percent had potential for severe or moderate harm.

“Those kind of things happen all the time,” said Gretchen M. Brophy, Pharm.D., professor of pharmacotherapy and outcomes science and neurosurgery at the VCU School of Pharmacy. Brophy is also a practicing neurocritical care clinical pharmacist at VCU Health and president of the national Neurocritical Care Society.

She offered an example: “A patient might go into a seizure in the emergency department and no one knows why,” Brophy said. “It turns out he is supposed to be on anticonvulsant or anti-epilepsy drugs, but he no longer has the medication in his system.”

The process of ferreting out which medicines are affecting patient health is called medication reconciliation. It is an important part of health care in general. In emergencies, the mystery can rise to a crisis level.

Standard blood tests for medications can take up to two weeks to process. Emergency department physicians, sometimes making decisions in seconds, need answers quickly.

With more than 130 million emergency department visits a year in the U.S. — 12 million of them serious enough to warrant hospital admission, according to the U.S. Centers for Disease Control and Prevention — a lot of patients are potentially at risk for dangerous medication interactions.

A SCIEX mass spectrometer. (Photo courtesy of SCIEX)
A SCIEX mass spectrometer. (Photo courtesy of SCIEX)

A new approach

A few years ago, the situation got Jayaraman thinking. How can modern emergency medicine, with its wondrous technology, still be using the same medication-reconciliation techniques it has for centuries — even as drugs have become more common? It was like a modern crime-scene investigator forced to use 18th-century technology rather than current forensic science.

Jayaraman, an associate professor of surgery in the School of Medicine, mentioned the mystery to a colleague, Dayanjan “Shanaka” Wijesinghe, Ph.D., an assistant professor in the Department of Pharmacotherapy and Outcomes Science at the VCU School of Pharmacy.

Wijesinghe was intrigued: “Basically, the doctors are working blind when it comes to medications,” he said.

But Wijesinghe quickly connected the issue to a technology he knew well. “I told her, ‘We have been doing this in the lab for a long time,’” he recalled.

The technology was mass spectrometry.

Mass spectrometry is a term used to describe an umbrella of technologies that allow the identification of a molecule by measuring its mass and then breaking those molecules apart and also measuring the masses of the fragmented components. The information gleaned from the technology can be compared to a database of intact and fragmented component masses of known compounds of interest to find the identity of the mystery molecule.

With this approach in mind, Wijesinghe and Jayaraman obtained grants from VCU’s C. Kenneth and Dianne Wright Center for Clinical and Translational Research and the Commercialization Fund, which is intended to advance VCU inventions to a more mature stage and improve their chances of being brought to market. Their objective was to assess the feasibility of using mass spectrometry in a clinical setting. With support from VCU Innovation Gateway, they have applied for a patent on the application and set up a company to market it, Mass Diagnostix.

In this early phase, the project aims to catalog 50 common drugs; so far, they have molecular signatures for 45, Wijesinghe said.

The future of patient care?

The interdisciplinary VCU team hopes the use of mass spectrometry to analyze patients’ medications will become common practice. They predict in a few years, use of the machines — which cost about $500,000 — will be standard practice for hospital laboratories.

The next step will be to expand the catalog of molecular signatures to many more medications — at least 100, Jayaraman said.

Wijesinghe suggests other possible uses. For example, he said, these instruments could record subtle changes in patients’ metabolisms that could predict life-threatening health crises before they happen.

Jayaraman and Wijesinghe are among the co-authors of a recent paper in the medical journal Shock that examines the possibility that mass spectrometry, along with other tests, could reduce deaths from trauma and its ensuing complications. Almost 200,000 trauma-related deaths occur every year in the U.S., most as a result of complications arising after the injury itself.

If this expansion of the technology into diagnosing future problems proves fruitful — and the researchers caution that years of study remain before that is determined — the effort to solve the mystery of what medications hide inside a patient’s body could have major advantages.

“We are hoping that this test will improve patient care,” Jayaraman said.

Pharmacy students present at pharmacoeconomics conference, win best poster award

Clockwise from top left: Students Yiran Zhang, Hrishikesh Kale and Purva Parab presented posters; adviser Norman Carroll and Kale with the winning poster; Carroll and students Zhang, Elena Fernandez, Parab, Kale, Batul Electricwala and Tim Inocencio at an alumni dinner; the VCU-ISPOR Team at the student research-quiz competition.

By Purva Parab (VCU-ISPOR Chapter President 2017-2018)

Hrishikesh Kale, a fourth-year Ph.D. candidate in the VCU School of Pharmacy, received the Best Student Poster Research Presentation Award at the recent conference of the International Society for Pharmacoeconomics and Outcomes Research.

The top 10 percent of posters out of 1,600 submitted were considered for the award this year; three including Kale received the award. Kale won for his poster, “Economic Burden of Renal Cell Carcinoma among Older Adults in the Targeted Therapy Era.” His adviser is Dr. Norman Carroll.

Other VCU School of Pharmacy students presenting posters at the conference include second-year master’s student Purva Parab (“Patterns of Use and Quality of Life Associated with the Utilization of Antidepressants amongst Cancer Patients with Depression”), whose adviser is Dr. Pramit Nadpara; and Yiran Zhang (“Transplanting Kidneys from HCV Positive Donors Into HCV Negative Recipients in the Era of Direct Acting Antiviral Therapy: A Cost Effectiveness Analysis”), a second-year VCU-Indivior fellow currently working with Carroll.

Graduate students from the Department of Pharmacotherapy and Outcomes Science (Division of Pharmacoeconomics and Health Outcomes) and the members of the VCU chapter of the International Society for Pharmacoeconomics and Outcomes Research represent the VCU School of Pharmacy every year and exhibit their research at the ISPOR international annual conference. (Read about some previous years’ conferences here and here.)

This year’s annual meeting was held in Baltimore. More than 4,000 people from more than 40 countries attended the conference, whose theme was “Real-World Evidence, Digital Health, and the New Landscape for Health Decision Making.”

The VCU-ISPOR team included Kale, Parab, Zhang and Ph.D. student Elena Fernandez.

VCU-ISPOR students chapter also hosted a VCU alumni dinner at the conference. Parab, the president of VCU-ISPOR chapter, received funding for the alumni dinner from the VCU development office.

“We would like to thank [former School of Pharmacy development director] Ellen Carfagno for arranging the funds for the dinner,” Parab said. “It was great!”

Promotions for School of Pharmacy faculty

Congratulations to the following faculty members on their promotions, effective July 1st, 2018. The promotions were approved by the VCU Board of Visitors at its most recent meeting.

Dr. Karolina Aberg has been promoted to associate professor in the Department of Pharmaceutics.
Dr. Krista Donohoe has been promoted to associate professor in the Department of Pharmacotherapy and Outcomes Science.
Dr. Keith Ellis has been promoted to associate professor in the Department of Medicinal Chemistry. He has also been awarded tenure.
Dr. Emily Peron has been promoted to associate professor in the Department of Pharmacotherapy and Outcomes Science.
Dr. Masahiro Sakagami has been promoted to professor with tenure in the Department of Pharmaceutics.

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