Author: ksas

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BE Seminar: “Predicting the Effects of Engineering Immune Cells Using Systems Biology Modeling” (Stacey Finley, USC)

The Penn Bioengineering virtual seminar series continues on October 1st.

Stacey Finley, PhD

 

Speaker: Stacey Finley, Ph.D.
Gordon S. Marshall Early Career Chair and Associate Professor of Biomedical Engineering and Biological Sciences
University of Southern California

 

Date: Thursday, October 1, 2020
Time: 3:00-4:00 pm
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Predicting the Effects of Engineering Immune Cells Using Systems Biology Modeling”

Abstract:

Systems biology approaches, including computational models, provide a framework to test biological hypotheses and optimize effective therapeutic strategies to treat human diseases. In this talk, I present recent work in modeling signaling in cancer-targeting immune cells, including CAR T cells at Natural Killer cells. Chimeric antigen receptors (CARs) are comprised of a variety of different activating domains and co-stimulatory domains that initiate signaling required for T cell activation. There is a lack of understanding of the mechanisms by which activation occurs. We apply mathematical modeling to investigate how CAR structure influences downstream T cell signaling and develop new hypotheses for the optimal design of CAR-engineered T cell systems. Natural Killer cells also provide a useful platform for targeting cancer cells. However, NK cells have been shown to exhibit reduced killing ability with prolonged stimulation by cancer cells. We use a combination of mechanistic model, optimal control theory and in silico synthetic biology to investigate strategies to enhance NK cell-mediated killing.

Bio:

Stacey D. Finley is the Gordon S. Marshall Early Career Chair and Associate Professor of Biomedical Engineering at the University of Southern California. Dr. Finley received her B.S. in Chemical Engineering from Florida A & M University and obtained her Ph.D. in Chemical Engineering from Northwestern University. She completed postdoctoral training at Johns Hopkins University in the Department of Biomedical Engineering. Dr. Finley joined the faculty at USC in 2013, and she leads the Computational Systems Biology Laboratory. Dr. Finley has joint appointments in the Departments of Chemical Engineering and Materials Science and Biological Science, and she is a member of the USC Norris Comprehensive Cancer Center. Dr. Finley is also the Director of the Center for Computational Modeling of Cancer at USC. Her research is supported by grants from NSF, NIH, and the American Cancer Society.

Selected honors: 2016 NSF Faculty Early CAREER Award; 2016 Young Innovator by the Cellular and Molecular Bioengineering journal; Leah Edelstein-Keshet Prize from the Society of Mathematical Biology; Junior Research Award from the USC Viterbi School of Engineering; the Hanna Reisler Mentorship Award; 2018 AACR NextGen Star; 2018 Orange County Engineering Council Outstanding Young Engineer

See the full list of upcoming Penn Bioengineering fall seminars here.

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Gardening in Costa Rica Yields Inspiration During Quarantine

by Isabella Lopez

María Suarez in her garden.

When the coronavirus pandemic began in March, María Suarez, junior in bioengineering, left Penn’s campus and returned home to Costa Rica. What should have been the final weeks of club activities, social events and end-of-year celebrations shifted to months spent at home, far away from Philadelphia. But Suarez, like many others, wanted to do something productive with her time in quarantine. Drawing on her bucolic roots, she decided to start a garden.

“I was born and raised in a very rural area,” Suarez says. “There is a huge river in my backyard where I learned how to count by throwing pebbles in the river with my mother and sister. Nature is a big part of my life, and it’s really shaped my personality. As a child, I planted herbs, like basil, mint and oregano, with my parents. When you are close to the land like this, gardening was something that grew naturally out of our lifestyle.”

As the spring semester shifted into summer, Suarez returned to her love of planting and embarked on an ambitious project to grow a vegetable garden in her backyard. Unlike the smaller herb gardens she had grown as a child, this vegetable garden required deeper horticultural knowledge as well as intense work under the hot sun.

“To begin the garden, I had to clear the land I wanted to use and remove all the grass and stones from the soil,” Suarez shares. “It was the dry season in Costa Rica and the ground was very difficult to work with.”

After clearing the land, Suarez had to bring nutrients back into the soil of her garden plot. Luckily, her family has been maintaining a natural compost pile for many years.

“Basically, the compost pile is a hole in the ground where we put our natural food waste. There are worms and animals there that help us naturally decompose the waste and they produce a very nutrient rich soil.” Suarez explains. “The compost is a five-minute walk from my garden, and I had to take at least ten trips with a wheelbarrow to bring enough back. It was a great arm workout.”

Once the soil was placed and watered, Suarez was finally able to plant her seeds. After a few days, she saw celery and zucchini plants beginning to sprout. Throughout the summer, Suarez’s crops grew well, and she was able to harvest the vegetables and share them with her family.

“It was very fulfilling to see the products of my efforts,” Suarez says.

Read the full story on the Penn Engineering blog.

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BE Seminar: “Patients, Providers and Data: How the EMR and Data Science are Changing Clinical Care” (Kevin Johnson, Vanderbilt)

The Penn Bioengineering virtual seminar series continues on September 24th.

Kevin Johnson, MD, MS

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 ksas@seas.upenn.edu

Title: “Patients, Providers and Data: How the EMR and Data Science are Changing Clinical Care”

Abstract:

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.

Bio:

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.

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MINS/BE Seminar: “Mapping emotions: discovering structure in mesoscale electrical brain recordings” (Kafui Dzirasa, Duke University)

The Mahoney Institute for Neurosciences (MINS) and Department of Bioengineering will co-host a seminar on September 16. Details and registration information are below. We hope you will join us to hear this upcoming talk.

Title: “Mapping emotions: discovering structure in mesoscale electrical brain recordings”

Kafui Dzirasa, MD, PhD

Speaker: Kafui Dzirasa,MD, PhD
K. Ranga Rama Krishnan Endowed Associate Professor
Department of Psychiatry and Behavioral Sciences
Duke University Medical Center

 

 

 

Date: Wednesday, September 16, 2020
Time: 4:00-5:30 PM Eastern Time
This event will be held virtually via Bluejeans (link here)

Hosted by Danielle Bassett and Joshua Gold

 

 

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Avery Posey’s cancer research takes high risks for big rewards

by Melissa Moody

Avery Posey, PhD (Image: Penn Medicine Newsby Melissa Moody

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.

Read more at Penn Medicine News.

N.B.: Avery Posey and Carl June are members of the Department of Bioengineering Graduate Group. Learn more about BE’s Grad Group Faculty here.

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Penn Bioengineering’s Tsourkas Lab and Penn Start-up AlphaThera Awarded $667,000 SBIR Phase II Grant to Improve COVID-19 Detection Assays

To combat the COVID-19 pandemic caused by the SARS-CoV2 virus, Dr. Andrew Tsourkas’s Targeted Imaging Therapeutics and Nanomedicine (Titan) Lab in Penn Bioengineering, in collaboration with the Penn-based startup, AlphaThera, was recently awarded a $667,000 SBIR Phase II Grant Extension to support its efforts in commercializing COVID-19 detection technology. The grant supports work to address the growing need for anti-viral antibody testing. Specifically, the Tsourkas Lab and AlphaThera hope to leverage their expertise with antibody conjugation technologies to reduce the steps and complexity of existing detection assays to enable greater production and higher sensitivity tests. AlphaThera was founded in 2016 by Andrew Tsourkas, PhD, Professor of Bioengineering and James Hui, MD, PhD, a graduate of the Perelman School of Medicine and Penn Bioengineering’s doctoral program.

During this pandemic it is crucial to characterize disease prevalence among populations, understand immunity, test vaccine efficacy and monitor disease resurgence. Projections have indicated that millions of daily tests will be needed to effectively control the virus spread. One important testing method is the serological assay: These tests detect the presence of SARS-CoV2 antibodies in a person’s blood produced by the body’s immune system responding to infection. Serological tests not only diagnose active infections, but also establish prior infection in an individual, which can greatly aid in forecasting disease spread and contact tracing. To perform the serological assays for antibody detection, well-established immunoassay methods are used such as ELISA.

A variety of issues have slowed the distribution of these serological assays for antibody testing. The surge in demand for testing has caused shortages in materials and reagents that are crucial for the assays. Furthermore, complexity in some of the assay formats can slow both production and affect the sensitivity of test results. Recognizing these problems, AlphaThera is leveraging its novel conjugation technology to greatly improve upon traditional assay formats.

With AlphaThera’s conjugation technology, the orientation of antibodies can be precisely controlled so that they are aligned and uniformly immobilized on assay detection plates. This is crucial as traditional serological assays often bind antibodies to plates in a non-uniform manner, which increases variability of results and reduces sensitivity. See Fig 1 below. With AlphaThera’s uniform antibody immobilization, assay specificity could increase by as much as 1000- fold for detection of a patient’s SaRS-CoV2 antibodies.

Fig 1: Uniform vs Non-Uniform Immobilized Antibodies on Surface: Top is AlphaThera improvement, showing how antibodies would be uniformly immobilized and oriented on a plate for detection. Bottom is how many traditional serological assays immobilize antibodies, resulting in variability of results and lower specificity.

Furthermore, AlphaThera is addressing the shortage of assay reagents, specifically secondary antibody reagents, by removing certain steps from traditional serological assays. Rather than relying on secondary antibodies for detection of the patient antibodies, AlphaThera’s technology can label the patient SaRS-CoV2 primary antibodies directly in serum with a detection reagent. This eliminates several processing steps, reducing the time of the assay by as much as 50%, as well as the costs.

The Tsourkas Lab and AlphaThera have initiated their COVID-19 project, expanding into the Pennovation Center and onboarding new lab staff. Other antibody labeling products have also become available and are currently being prepared for commercialization. Check out the AlphaThera website to learn more about their technology at https://www.alphathera.com.

NIH SBIR Phase II Grant Extension— 5-R44-EB023750-03 (PI: Yu)  — 10/07/2020 – 10/07/2021

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BE Seminar: “Stem Cell Fate is a Touchy Subject” (Quinton Smith, MIT)

The first lecture in the Fall 2020 Penn Bioengineering Seminar Series will be held Thursday, September 10th. All seminars this semester will be held virtually on Zoom.

Quinton Smith, PhD

Speaker: Quinton Smith, Ph.D.
Postdoctoral Fellow
Laboratory for Multiscale Regenerative Technologies
Massachusetts Institute of Technology

Date: Thursday, September 10, 2020
Time: 3:00-4:00 pm
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Stem Cell Fate is a Touchy Subject”

Abstract:

The success of regenerative cell therapy relies on the integration of a functional vascular system within the redeveloping tissue, to mediate the exchange of oxygen, nutrients and waste. Although the advent of human induced pluripotent stem cells (hiPSCs) has accelerated progress towards this goal, owing to their potential to generate clinically relevant scales of patient-specific cells, techniques to drive their specification mainly rely on chemical cues. In this seminar, I will discuss engineering strategies to control the complex stem cell extracellular milieu, emphasizing the importance of mechanical cues during hiPSC development, specification and downstream functionality as it relates to vascular differentiation.

Bio:

Quinton Smith received his PhD in Chemical and Biomolecular Engineering from Johns Hopkins University in 2017 after completing his bachelor’s degree in Chemical Engineering from the University of New Mexico. As a graduate student under the guidance of Dr. Sharon Gerecht, Quinton implemented various engineering tools to explore the roles of physical and chemical cues on stem cell lineage specification and downstream maturation. Dr. Smith is currently a postdoctoral fellow under the mentorship of Dr. Sangeeta Bhatia at MIT’s Koch Institute for Integrative Cancer Research, where he is investigating the role biliary epithelium in liver regeneration. Dr. Smith’s predoctoral work was supported by an NIH/NHLBI F-31 and NSF Graduate Research Fellowship. He is a recipient of the 2017 Siebel Scholar award, and most recently joined the class of 2018 HHMI Hanna Gray Fellows.

See the full list of upcoming Penn Bioengineering fall seminars here.

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Jennifer Phillips-Cremins Wins CZI Grant to Study 3D Genome’s Role in Neurodegenerative Disease

The Chan Zuckerberg Initiative’s Collaborative Pairs Pilot Project Award is part of its Neurodegeneration Challenge Network

Jennifer Phillips-Cremins, Ph.D.

Read the full story on the Penn Engineering blog.

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Danielle Bassett on ‘A Radical New Model of the Brain’

In a ‘Wired’ feature, Bassett helps explain the growing field of network neuroscience and how the form and function of the brain are connected.

Danielle Bassett, Ph.D.

Early attempts to understand how the brain works included the pseudoscience of phrenology, which theorized that various mental functions could be determined through the shape of the skull. While those theories have long been debunked, modern neuroscience has shown a kernel of truth to them: those functions are highly localized to different regions of the brain.

Now, Danielle Bassett, Professor of J. Peter Skirkanich Professor of Bioengineering and Electrical and Systems Engineering, is pioneering a new subfield that goes even deeper into the connection between the brain’s form and function: network neuroscience.

In a recent feature article in Wired, Bassett explains the concepts behind this new subfield. While prior understanding has long relied on the idea that certain areas of the brain control certain functions, Bassett and other network neuroscientists are using advances in imaging and machine learning to reveal the role the connections between those areas play.

For Bassett, one of the first indicators that these connections mattered more than previously realized was the shape of the neurons themselves.

Speaking with Wired’s Grace Huckins, Bassett says:

“Neurons are not spherical — neurons have a cell body, and then they have this long tail that allows them to connect to many other cells. You can even look at the morphology of the neuron and say, ‘Oh, well, connectivity has to matter. Otherwise, it wouldn’t look like this.’”

Read more about Bassett and the field of network neuroscience in Wired.

Originally posted on the Penn Engineering blog.

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Meet Bioengineering Sophomore and SNF Paideia Fellow Catherine Michelutti

Catherine Michelutti (BSE, BS ’23)

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).

Read more about Catherine and other Fellows on the SNF Paideia Instagram.