Brian Litt, professor in Engineering’s Department of Bioengineering and the Perelman School of Medicine’s departments of Neurology and Neurosurgery, has received a five-year, $5.6 million Pioneer Award from the National Institutes of Health, which will support his research on implantable devices for monitoring, recording and responding to neural activity.
The Pioneer Award is part of the agency’s High-Risk, High-Reward Research Program honoring exceptionally creative scientists. It challenges investigators to pursue new research directions and develop groundbreaking, high-impact approaches to a broad area of biomedical or behavioral science. Litt’s neurodevice research represents a new frontier in addressing a wide variety of neurological conditions.
In epilepsy, for example, these devices would predict and prevent seizures; in Parkinson’s patients, implants will measure and communicate with patients to improve mobility, reduce tremor and enhance responsiveness. Other implants might improve hearing or psychiatric symptoms by querying patient perceptions, feelings, and altering stimulation patterns algorithmically to improve them
Single cell sequencing aided researchers in identifying a previously undiscovered molecule in the brain.
Chimeric antigen receptor (CAR) T cell therapy has revolutionized treatment of leukemia, lymphoma, and multiple myeloma. But some people who have received this treatment experience neurotoxicity, or damage to the brain or nervous system.
New research from a team led by Avery Posey, an assistant professor of systems pharmacology and translational therapeutics in the Perelman School of Medicine, provides evidence that this side effect may owe to a molecule in the brain that scientists previously didn’t know was there.
The work, published in the journal Cell, revealed that the protein CD19 is present in brain cells that protect the blood-brain barrier. Prior to the finding, scientists believed CD19 was only expressed on B cells, and the protein served as a target for certain forms of CAR-T therapy. The discovery may chart a path forward for new strategies to effectively treat cancer while sparing the brain.
“The next question is,” says Posey, “can we identify a better target for eliminating B cell related malignancies other than CD19, or can we engineer around this brain cell expression of CD19 and build a CAR T cell that makes decisions based on the type of cell it encounters—for instance, CAR T cells that kill the B cells they encounter, but spare the CD19 positive brain cells?”
The Penn Bioengineering virtual seminar series continues on September 24th.
Speaker: Kevin Johnson, M.D., M.S.
Cornelius Vanderbilt Professor and Chair
Department of Biomedical Informatics
Vanderbilt University Medical Center
Date: Thursday, September 24, 2020
Time: 3:00-4:00 pm
Zoom – check email for link or contact firstname.lastname@example.org
Title: “Patients, Providers and Data: How the EMR and Data Science are Changing Clinical Care”
The electronic health record (EHR) is a powerful application of Systems Engineering to healthcare. It is a byproduct of a host of pressures including cost, consolidation of providers into networks, uniform drivers of quality, and the need for timely care across disparate socioeconomic and geographic landscapes within health systems. The EHR is also a fulcrum for innovation and one of the most tangible examples of how data science affects our health and health care. In this talk I will showcase projects from my lab that demonstrate the multi-disciplinary nature of biomedical informatics/data science research and translation using the EHR, and our current understanding of its potential from my perspective as a pediatrician, a researcher in biomedical informatics, a Chief Information Officer, an educator, and an advisor to local and international policy. I will describe advances in applying human factors engineering to support medical documentation and generic prescribing, approaches to improve medication safety, and innovations to support precision medicine and interoperability. I will present our efforts to integrate EHR-enabled data science into the Vanderbilt health system and provide a vision for what this could mean for our future.
Kevin B. Johnson, M.D., M.S. is Informatician-in-Chief, Cornelius Vanderbilt Professor and Chair of Biomedical Informatics, and Professor Pediatrics at Vanderbilt University Medical Center. He received his M.D. from Johns Hopkins Hospital in Baltimore and his M.S. in Medical Informatics from Stanford University. In 1992 he returned to Johns Hopkins where he served as a Pediatric Chief Resident. He was a member of the faculty in both Pediatrics and Biomedical Information Sciences at Johns Hopkins until 2002, when he was recruited to Vanderbilt University. He also is a Board-Certified Pediatrician.
Dr. Johnson is an internationally respected developer and evaluator of clinical information technology. His research interests have been related to developing and encouraging the adoption of clinical information systems to improve patient safety and compliance with practice guidelines; the uses of advanced computer technologies, including the Worldwide Web, personal digital assistants, and pen-based computers in medicine; and the development of computer-based documentation systems for the point of care. In the early phases of his career, he directed the development and evaluation of evidence-based pediatric care guidelines for the Johns Hopkins Hospital. He has been principal investigator on numerous grants and has been an invited speaker at most major medical informatics and pediatrics conferences. He also was the Chief Informatics Officer at Vanderbilt University Medical Center from 2015-2019.
See the full list of upcoming Penn Bioengineering fall seminars here.
Much of the world, including research at Penn Medicine, has focused its attention on how T cells–which play a central role in immune response—might shape the trajectory of COVID-19 infection, and how immunotherapy can shed light on treatment of the disease.
Already a leader in immunotherapy research and treatment, Penn Medicine pioneered the groundbreaking development of CAR T cell cancer therapy. Avery Posey, an assistant professor of systems pharmacology and translational therapeutics, trained as a postdoctoral fellow in the lab of Carl June, who pioneered CAR T cell immunotherapy to treat cancer. Now as a faculty member at Penn, Posey has maintained a focus on T cell therapeutics, mostly for the treatment of cancer.
“This research combines two of my biggest interests—the use of gene therapy to treat disease and the investigation of little known biology, such as the roles of glycans in cell behavior. The pursuit of new knowledge, the roads less traveled—those are my inspirations,” Posey says.
Rising Bioengineering Sophomore Catherine Michelluti (BSE 2023) has been featured on Penn’s SNF Paideia Program Instagram which discusses her diverse interests in machine learning in medicine, computer science, playing the violin and more. Catherine is a pre-med student who is pursuing an uncoordinated dual degree between the School of Engineering and Applied Science and the Wharton School of Business (BS in Economics 2023). She is also an incoming fellow in the SNF Paideia Program, which is supported by the Stavros Niarchos Foundation, is an interdisciplinary program which “encourage[s] the free exchange of ideas, civil and robust discussion of divergent views, and the integration of individual and community wellness, service, and citizenship through SNF Paideia designated courses, a fellows program, and campus events” (SNF Paideia website).
The paper-based tests could be integrated directly into facemasks and provide instant results at testing sites.
When Penn Health-Tech announced its Nemirovsky Engineering and Medicine Opportunity, or NEMO Prize, in February, the center’s researchers could only begin to imagine the impact the looming COVID-19 pandemic was about to unleash. But with the promise of $80,000 to support early-stage ideas at the intersection of engineering and medicine, the contest quickly sparked a winning innovation aimed at combating the crisis.
Judges from the University of Pennsylvania’s School of Engineering and Applied Sciences and Perelman School of Medicine awarded its first NEMO Prize to César de la Fuente, PhD, who proposed a paper-based COVID diagnostic system that could capture viral particles on a person’s breath, then give a result in a matter of seconds when taken to a testing site.
Similar tests for bacteria cost less than a dollar each to make. De la Fuente, a Presidential Assistant Professor in the departments of Psychiatry, Microbiology, and Bioengineering, is aiming to make COVID tests at a similar price point and with a smaller footprint so that they could be directly integrated into facemasks, providing further incentive for their regular use.
“Wearing a facemask is vital to containing the spread of COVID because, before you know you’re sick, they block your virus-carrying droplets so those droplets can’t infect others,” de la Fuente says. “What we’re proposing could eventually lead to a mask that can be infected by the virus and let you know that you’re infected, too.”
De la Fuente’s expertise is in synthetic biology and molecular-scale simulations of disease-causing viruses and bacteria. Having such fine-grained computational models of these microbes’ binding sites allow de la Fuente to test them against massive libraries of proteins, seeing which bind best. Other machine learning techniques can then further narrow down the minimum molecular structures responsible for binding, resulting in functional protein fragments that are easier to synthesize and manipulate.
The spike-shaped proteins that give coronaviruses their crown-like appearance and name bind to a human receptor known as ACE2. De la Fuente and his colleagues are now aiming to characterize the molecular elements and environmental factors that would allow for the most precise, reliable detection of the virus.
Huwe earned dual B.S. degrees in Biology and Chemistry in 2009 from Mississippi College, where he was inducted into the Hall of Fame. At Mississippi College, Huwe had his first exposure to computational research in the laboratory of David Magers, Professor of Chemistry and Biochemistry. He went on to earn his Ph.D. in Biochemistry and Molecular Biophysics in 2014 in the laboratory of Ravi Radhakrishnan, Chair of the Bioengineering Department at Penn. As an NSF Graduate Research Fellow in Radhakrishnan’s lab, Huwe focused his research on using computational molecular modeling and simulations to elucidate the functional consequences of protein mutations associated with human diseases. Dr. Huwe then joined the structural bioinformatics laboratory Roland Dunbrack, Jr., Professor at the Fox Chase Cancer Center as a T32 post-doctoral trainee. During his post-doctoral training, Huwe held adjunct teaching appointments at Thomas Jefferson University and at the University of Pennsylvania. In 2017, Huwe became an Assistant Professor of Biology at Temple University, where he taught medical biochemistry, medical genetics, cancer biology, and several other subjects.
During each of his appointments, Huwe became increasingly more passionate about teaching, and he decided to dedicate his career to medical education. Huwe is very excited to be joining Mercer University School of Medicine as an Assistant Professor of Biomedical Sciences this summer. There, he will serve in a medical educator track, primarily teaching first and second year medical students.
“Without Ravi Radhakrishnan and Philip Rea, Professor of Biology in Penn’s School of Arts & Sciences, giving me my first teaching opportunities as a graduate guest lecturer at Penn, I may never have discovered how much I love teaching,” says Huwe. “And without the support and guidance of each of my P.I.’s [Dr.’s Magers, Radhakrishnan, and Dunbrack], I certainly would not be where I am, doing what I love. I am incredibly thankful for all of the people who helped me in my journey to find my dream job.”
Congratulations and best of luck from everyone in Penn Bioengineering, Dr. Huwe!
Hammer will offer a course on COVID-19 and the coronavirus pandemic during Penn’s Summer II session, which will be held online this year. The course will be co-taught with Miriam Wattenbarger, senior lecturer in CBE.
The course, “Biotechnology, Immunology, and COVID-19,” will culminate with a case study of the coronavirus pandemic including the types of drugs proposed and their mechanism of action, as well as the process of vaccine development.
“Obviously, the pandemic has been a life-altering event, causing an immense dislocation for everyone in our community, especially the students. Between me and Miriam, who has been trumpeting the importance of vaccines for some time in her graduate-level CBE courses, we have the expertise to inform students about this disease and how we might combat it,” says Hammer.
For more than ten years, Wattenbarger has run courses and labs focused on drug delivery and biotechnology, key elements of the vaccine development process.
“I invite both researchers and industry speakers to meet with my students,” Wattenbarger says, “so that they learn the crucial role engineers play in both vaccine development and manufacturing.”
Beyond studying the interactions between the immune system and viruses — including HIV, influenza, adenovirus and coronavirus — students will cover a variety of biotechnological techniques relevant to tracking and defending against them, including recombinant DNA technology, polymerase chain reaction, DNA sequencing, gene therapy, CRISPR-Cas9 editing, drug discovery, small molecule inhibitors, vaccines and the clinical trial process.
Students will also learn the mathematical principles used to quantify biomolecular interactions, as well as those found behind simple epidemiological models and methods for making and purifying drugs and vaccines.
“We all have to contribute in the ways that we can. Having taught biotechnology to freshmen for the past decade, this is something that I can do that can both inform and build community,” says Hammer. “Never has it been more important to have an informed and scientifically literate community that can fight this or any future pandemic.”
A blood test may be able to detect the most common form of pancreatic cancer while it is still in its early stages while also helping doctors accurately stage a patient’s disease and guide them to the appropriate treatment. A multidisciplinary study found the test—known as a liquid biopsy—was more accurate at detecting disease in a blinded study than any other known biomarker alone, and was also more accurate at staging disease than imaging is capable of alone. The team, which includes researchers from the Perelman School of Medicine, the Abramson Cancer Center, and the School of Engineering and Applied Science, published their findings in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is the third leading cause of cancer deaths. The overall five-year survival rate is just 9%, and most patients live less than one year following their diagnosis. One of the biggest challenges is catching the disease before it has progressed or spread. If the disease is caught early, patients may be candidates for surgery to remove the cancer, which can be curative. For locally advanced patients—meaning patients whose cancer has not spread beyond the pancreas but who are not candidates for surgery based on the size or location of the tumor—treatment involves three months of systemic therapy like chemo or radiation, then reassessing to see if surgery is an option. For patients whose disease has spread, there are currently no curative treatment options.
“Right now, the majority of patients who are diagnosed already have metastatic disease, so there is a critical need for a test that can not only detect the disease earlier but also accurately tell us who might be at a point where we can direct them to a potentially curative treatment,” says the study’s co-senior author Erica L. Carpenter,director of the Liquid Biopsy Laboratory and a research assistant professor of medicine. The study’s other co-senior author is David Issadore, an associate professor of bioengineering and electrical and systems engineering.