Tag: biophysics

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More Cancers May be Treated with Drugs than Previously Believed

by Alex Gardner

3D illustration of cancer cells
nucleus and membrane of pathogen micro organisms in blue background

Up to 50 percent of cancer-signaling proteins once believed to be immune to drug treatments due to a lack of targetable protein regions may actually be treatable, according to a new study from the Perelman School of Medicine at the University of Pennsylvania. The findings, published this month in Nature Communications, suggest there may be new opportunities to treat cancer with new or existing drugs.

Researchers, clinicians, and pharmacologists looking to identify new ways to treat medical conditions—from cancer to autoimmune diseases—often focus on protein pockets, areas within protein structures to which certain proteins or molecules can bind. While some pockets are easily identifiable within a protein structure, others are not. Those hidden pockets, referred to as cryptic pockets, can provide new opportunities for drugs to bind to. The more pockets scientists and clinicians have to target with drugs, the more opportunities they have to control disease.

The research team identified new pockets using a Penn-designed neural network, called PocketMiner, which is artificial intelligence that predicts where cryptic pockets are likely to form from a single protein structure and learns from itself. Using PocketMiner—which was trained on simulations run on the world’s largest super computer—researchers simulated single protein structures and successfully predicted the locations of cryptic pockets in 35 cancer-related protein structures in thousands of areas of the body. These once-hidden targets, now identified, open up new approaches for potentially treating existing cancer.

What’s more, while successfully predicting the cryptic pockets, the method scientists used in this study was much faster than previous simulation or machine-learning methods. The network allows researchers to nearly instantaneously decide if a protein is likely to have cryptic pockets before investing in more expensive simulations or experiments to pursue a predicted pocket further.

“More than half of human proteins are considered undruggable due to an apparent lack of binding proteins in the snapshots we have,” said Gregory R. Bowman, PhD, a professor of Biochemistry and  Biophysics and Bioengineering at Penn and the lead author of the study. “This PocketMiner research and other research like it not only predict druggable pockets in critical protein structures related to cancer but suggest most human proteins likely have druggable pockets, too. It’s a finding that offers hope to those with currently untreatable diseases.”

Read the full story in Penn Medicine News.

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Penn Bioengineering Alumna Cynthia Reinhart-King is President Elect of BMES

Dr. Cynthia Reinhart-King, Engineering, BME, Photo by Joe Howell

Penn Bioengineering alumna Cynthia Reinhart-King, Cornelius Vanderbilt Professor of Engineering and Professor of Biomedical Engineering at Vanderbilt University, was elected the next President of the Biomedical Engineering Society (BMES), the largest professional society for biomedical engineers. Her term as president-elect started at the annual BMES meeting in October 2021.

Reinhart-King graduated with her Ph.D. from Penn Bioengineering in 2006. She studied in the lab of Daniel Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and Chemical and Biomolecular Engineering as a Whitaker Fellow and went on to complete postdoctoral training as an Individual NIH NRSA postdoctoral fellow at the University of Rochester. Prior to joining Vanderbilt, she was on the faculty of Cornell University and received tenure in the Department of Biomedical Engineering. The Reinhart-King lab at Vanderbilt “uses tissue engineering, microfabrication, novel biomaterials, model organisms, and tools from cell and molecular biology to study the effects of mechanical and chemical changes in tissues during disease progression.”

Reinhart-King gave the 2019 Grace Hopper Distinguished Lecture, sponsored by the Department of Bioengineering. This lecture series recognizes successful women in engineering and seeks to inspire students to achieve at the highest level. She is a recipient of numerous prestigious awards, including the Rita Schaffer Young Investigator Award in 2010, an NSF CAREER Award, and the Mid-Career Award in 2018 from BMES.

In a Q&A on the BMES Blog, Reinhart-King said that:

“BMES is facing many challenges, like many societies, as we deal with the hurdles associated with COVID-19 and inequities across society. We must continue to address those challenges. However, we are also in a terrific window of having robust membership, many members who are eager to get involved with the society’s activities, and a national lens on science and scientists. One of my goals will be to identify and create opportunities for our members to help build the reach of the society and its member.”

Read “Cynthia Reinhart-King is president-elect of the Biomedical Engineering Society” in Vanderbilt News.

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BE Seminar: “Dynamics of 3D Cell Migration and Organ Formation” (Kenneth Yamada)

Our next Penn Bioengineering seminar will be held on zoom next Thursday.

Kenneth Yamada, MD, PhD

Speaker: Kenneth Yamada, M.D., Ph.D.
NIH Distinguished Investigator
Cell Biology Section
National Institute of Dental and Craniofacial Research, National Institutes of Health (NIH)

Date: Thursday, September 9, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Location: Moore Room 216, 200 S. 33rd Street

Abstract: Real-time microscopy of the dynamics of cells and tissues in 3D environments is opening new windows to understanding the biophysical mechanisms of complex biological processes. Direct visualization is allowing us to explore fundamental questions in more depth that include: How do cells migrate in 3D? How do cancer cells invade? How is the extracellular matrix assembled? How are organs formed? Visualizing how cells move and organize into tissues is not only providing descriptive insights, but is also leading to the identification of novel, unexpected physical and mechanical mechanisms relevant to tissue engineering. Cells can use varying combinations of cell adhesion to adjacent cells and to the surrounding extracellular matrix with localized cellular contractility to migrate, invade, and produce the complex tissue architecture needed for organ formation.

Kenneth Yamada Bio: Kenneth Yamada has been an NIH Distinguished Investigator since 2011. He received MD and PhD degrees from Stanford. He was a Section Chief at the National Cancer Institute for 10 years and has been a Section Chief at NIDCR since 1990. He is an elected Fellow of the AAAS and American Society for Cell Biology. His research focuses on discovering novel mechanisms and regulators of cell interactions with the extracellular matrix and their roles in embryonic development and cancer. His research group focuses on the mechanisms by which three-dimensional (3D) extracellular matrix mediates key biological events, including cell migration, tissue morphogenesis, and cancer cell invasion. His research places particular emphasis on characterizing the dynamic movements of cells and their extracellular matrix as tissues are remodeled in 3D in real time. The biological systems they study include human primary cells migrating in 3D, human tumor cells and tissues, and mouse organ development. He places particularly high priority on developing future independent research leaders.

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Seminar: “The Coming of Age of De Novo Protein Design” (David Baker)

David Baker, Ph.D.

Speaker: David Baker, Ph.D.
Professor
Biochemistry
University of Washington

Date: Thursday, March 18, 2021
Time: 3:00-4:00 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “The Coming of Age of De Novo Protein Design”

This seminar is jointly hosted by the Department of Bioengineering and the Department of Biochemistry & Biophysics.

Abstract:

Proteins mediate the critical processes of life and beautifully solve the challenges faced during the evolution of modern organisms. Our goal is to design a new generation of proteins that address current day problems not faced during evolution. In contrast to traditional protein engineering efforts, which have focused on modifying naturally occurring proteins, we design new proteins from scratch based on Anfinsen’s principle that proteins fold to their global free energy minimum. We compute amino acid sequences predicted to fold into proteins with new structures and functions, produce synthetic genes encoding these sequences, and characterize them experimentally. I will describe the de novo design of fluorescent proteins, membrane penetrating macrocycles, transmembrane protein channels, allosteric proteins that carry out logic operations, and self-assembling nanomaterials and polyhedra. I will also discuss the application of these methods to COVID-19 challenges.

Bio:

David Baker is the director of the Institute for Protein Design, a Howard Hughes Medical Institute Investigator, a professor of biochemistry and an adjunct professor of genome sciences, bioengineering, chemical engineering, computer science, and physics at the University of Washington. His research group is a world leader in protein design and protein structure prediction. He received his Ph.D. in biochemistry with Randy Schekman at the University of California, Berkeley, and did postdoctoral work in biophysics with David Agard at UCSF. Dr. Baker is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. Dr. Baker is a recipient of the Breakthrough Prize in Life Sciences, Irving Sigal and Hans Neurath awards from the Protein Society, the Overton Prize from the ISCB, the Feynman Prize from the Foresight Institute, the AAAS Newcomb Cleveland Prize, the Sackler prize in biophysics, and the Centenary Award from the Biochemical society. He has also received awards from the National Science Foundation, the Beckman Foundation, and the Packard Foundation. Dr. Baker has published over 500 research papers, been granted over 100 patents, and co-founded 11 companies. Seventy-five of his mentees have gone on to independent faculty positions.

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BE Seminar: “Imaging and Sequencing Single Cells” (Aaron Streets, UC Berkeley)

The Penn Bioengineering virtual seminar series continues on October 8th.

Aaron Streets, PhD

 

Speaker: Aaron Streets, Ph.D.
Associate Professor of Bioengineering
University of California, Berkeley

Date: Thursday, October 8, 2020
Time: 2:00-3:00 pm (note the change from our regular seminar time)
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Imaging and Sequencing Single Cells”

Abstract:

Recent advances in microfluidics and high-throughput sequencing technology have enabled rapid profiling of genomic material in single cells. Valve- and droplet-based microfluidic platforms can precisely and efficiently manipulate, sort, and process cells to generate indexed sequencing libraries, allowing for high-throughput single-cell analysis of the genome, transcriptome, proteome, and epigenome. Such technology has been instrumental in the global effort to create a human cell atlas, with the ambitious goal of identifying and cataloging all human cell types and cell states in health and disease. However, not all cell phenotypes are directly encoded in the genome and high-throughput sequencing cannot probe the full space of cellular identity. Therefore, microscopy remains one of the most powerful and versatile tools for characterizing cells. Fluorescent imaging and quantitative non-linear optical imaging can reveal morphological characteristics, protein localization, chromatin organization, and chemical composition in single cells. Both single-cell genomics and microscopy can uncover heterogeneity in cellular populations that would otherwise be obscured in ensemble measurement. In this talk, I will discuss a suite of new microfluidic platforms for coupling genomic measurements and optical measurements of the same single cell, and some novel computational approaches to grapple with these new datasets. With a combination of new hardware and software, our goal is to converge on a quantitative and comprehensive understanding of cellular identity.

Bio:

Aaron received a Bachelor of Science in Physics and a Bachelor of Arts in Art at UCLA. He completed his PhD in Applied Physics at Stanford with Dr. Stephen Quake. Aaron then went to Beijing, China as a Whitaker International Postdoctoral Fellow and a Ford postdoctoral fellow and worked with Dr. Yanyi Huang in the Biodynamic Optical Imaging Center (BIOPIC) at Peking University. Aaron joined the faculty of UC Berkeley as an Assistant Professor in Bioengineering in 2016 and is currently a core member of the Biophysics Program and the Center for Computational Biology and he is a Chan Zuckerberg Biohub investigator. Aaron has received the NSF Early Career award and was recently named a Pew Biomedical Scholar.

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

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Penn Alumnus Peter Huwe Appointed Assistant Professor at Mercer University

Peter Huwe, Ph.D.

Peter Huwe, a University of Pennsylvania alumnus and graduate of the Radhakrishnan lab, was appointed Assistant Professor of Biomedical Sciences at the Mercer University School of Medicine beginning this summer 2020 semester.

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!