news – Page 12 – Penn Bioengineering Blog

March 15, 2022

Bionegineering Spin-off Vivodyne on Fast Company’s ‘Most Innovative’ List

Andrei Georgescu (left) and Dan Huh developed several organ-on-a-chip platforms in Huh’s lab. Their spin-off company, Vivodyne, aims to use the technology as a scalable alternative to animal testing in the pharmaceutical industry.

With Vivodyne, Associate Professor in the Department of Bioengineering Dan Huh is translating the organs-on-chips technology into a promising industry venture. Using microfluidic structures that mimic aspects of human physiology, organs-on-chips allow scientists to test therapies on lab-grown human cells. Vivodyne specifically focuses on designing organs-on-chips to create a scalable alternative for pharmaceutical drug testing on animals.

Last year, the company raised $4 million dollars in seed money. This year, it’s topping influential lists of small companies making big impacts.

Fast Company now lists it as one of “the 10 most innovative companies with fewer than 10 employees,” saying “Vivodyne is helping major pharmaceutical companies like GlaxoSmithKline quickly adopt viable alternatives for testing drugs on monkeys.”

Vivodyne, launched in 2021, has created a platform that allows fully automated, complex studies at a far larger scale and lower cost than would be possible with manual experimentation, so pharmaceutical companies can actually test lab-made organs instead of animals in their drug-development processes. When done by hand, only 20 to 40 living tissue samples can be managed in parallel; Vivodyne’s instrument can cultivate, dose, and image more than 2,000 living tissues at once. The company, which raised $4 million in seed funding last year, says its instruments currently play pivotal roles in clinical drug testing for respiratory diseases, cancer treatment, vaccine development, diabetes therapies, and maternal medicine. GlaxoSmithKline, one of Vivodyne’s clients, estimates that for some projects the lab-grown tissues may displace as much as 80% of its animal testing. The company’s ultimate goal? “To supplant the vast majority of animal testing within the next decade,” says CEO Andrei Georgescu.

Continue reading “The 10 most innovative companies with fewer than 10 employees” at Fast Company.

Originally posted in Penn Engineering today.

March 3, 2022March 23, 2022

Konrad Kording Appointed Co-Director the CIFAR Learning in Machines & Brains Program

Konrad Kording, PhD (Photo by Eric Sucar)

Konrad Kording, Nathan Francis Mossell University Professor in Bioengineering, Neuroscience, and Computer and Information Sciences, was appointed the Co-Director of the CIFAR Program in Learning in Machines & Brains. The appointment will start April 1, 2022.

CIFAR is a global research organization that convenes extraordinary minds to address the most important questions facing science and humanity. CIFAR was founded in 1982 and now includes over 400 interdisciplinary fellows and scholars, representing over 130 institutions and 22 countries. CIFAR supports research at all levels of development in areas ranging from Artificial Intelligence and child and brain development, to astrophysics and quantum computing. The program in Learning in Machines & Brains brings together international scientists to examine “how artificial neural networks could be inspired by the human brain, and developing the powerful technique of deep learning.” Scientists, industry experts, and policymakers in the program are working to understand the computational and mathematical principles behind learning, whether in brains or in machines, in order to understand human intelligence and improve the engineering of machine learning. As Co-Director, Kording will oversee the collective intellectual development of the LMB program which includes over 30 Fellows, Advisors, and Global Scholars. The program is also co-directed by Yoshua Benigo, the Canada CIFAR AI Chair and Professor in Computer Science and Operations Research at Université de Montréal.

Kording, a Penn Integrates Knowledge (PIK) Professor, was previously named an associate fellow of CIFAR in 2017. Kording’s groundbreaking interdisciplinary research uses data science to advance a broad range of topics that include understanding brain function, improving personalized medicine, collaborating with clinicians to diagnose diseases based on mobile phone data and even understanding the careers of professors. Across many areas of biomedical research, his group analyzes large datasets to test new models and thus get closer to an understanding of complex problems in bioengineering, neuroscience and beyond.

Visit Kording’s lab website and CIFAR profile page to learn more about his work in neuroscience, data science, and deep learning.

March 1, 2022

Decade-long Remission After CAR T Cell Therapy

Bill Ludwig, left, was the first patient to receive CAR T cells as part of clinical trials at Abramson Cancer Center. Carl June, right, has played a pioneering roll in the therapeutic use of CAR T cells. (Image: Penn Medicine)

Carl H. June, the Richard W. Vague Professor in Immunotherapy in Pathology and Laboratory Medicine at Penn Medicine, director of the Center for Cellular Immunotherapies and the Parker Institute for Cancer Immunotherapy, and member of the Penn Bioengineering Graduate Group at the University of Pennsylvania, has led a new analytical study published in Nature that explains the longest persistence of CAR T cell therapy recorded to date against chronic lymphocytic leukemia (CLL), and shows that the CAR T cells remained detectable at least a decade after infusion, with sustained remission in both patients. June’s pioneering work in gene therapy led to the FDA approval for the CAR T therapy (sold by Novartis as Kymriah) for treating leukemia and transforming the fight against cancer. His lab develops new forms of T cell based therapies.

Read the story in Penn Today

February 22, 2022March 23, 2022

Jennifer Phillips-Cremins Wins ISSCR Dr. Susan Lim Award for Outstanding Young Investigator

Jennifer E. Phillips-Cremins, Associate Professor and Dean’s Faculty Fellow in Bioengineering and Genetics, has been awarded the 2022 Dr. Susan Lim Award for Outstanding Young Investigator by the International Society for Stem Cell Research (ISSCR), the preeminent, global organization dedicated to stem cells research.

This award recognizes the exceptional achievements of an investigator in the early part of his or her independent career in stem cell research. Cremins works in the field of epigenetics, and is a pioneer in understanding how chromatin, the substance within a chromosome, works:

“Dr. Phillips-Cremins is a gifted researcher with diverse skills across cell, molecular, and computational biology. She is a shining star in the stem cell field who has already made landmark contributions in bringing long-range chromatin folding mechanisms to stem cell research. In addition to her skills as an outstanding researcher,” ISSCR President Melissa Little, Ph.D., said. “She has flourished as an independent investigator, providing the stem cell field with unique and creative approaches that have facilitated conceptual leaps in our understanding of long-range spatial regulation of stem cell fate. Congratulations, Jennifer, on this prestigious honor.”

Cremins was awarded a NIH Director’s Pioneer Award in 2021 and a Chan Zuckerberg Initiative (CZI) grant as part of the CZI Collaborative Pairs Pilot Project in 2020. The long-term goal of her lab is to understand the mechanisms by which chromatin architecture governs genome function. The ISSCR will recognize Cremins and her research in a plenary session during the ISSCR annual meeting on June 15.

Read the full press release on the ISSCR website.

February 15, 2022

New Lipid Nanoparticles Improve mRNA Delivery for Engineering CAR T Cells

by Melissa Pappas

The Penn researchers’ latest paper on the design of lipid nanoparticles was featured on the cover of the most recent edition of the journal Nano Letters.

From COVID vaccines to cancer immunotherapies to the potential for correcting developmental disorders in utero, mRNA-based approaches are a promising tool in the fight against a wide range of diseases. These treatments all depend on providing a patient’s cells with genetic instructions for custom proteins and other small molecules, meaning that getting those instructions inside the target cells is of critical importance.

The current delivery method of choice uses lipid nanoparticles (LNPs). Thanks to surfaces customized with binding and signaling molecules, they encapsulate mRNA sequences and smuggle them through the cell membrane. But with a practically unlimited number of variables in the makeup of those surfaces and molecules, figuring out how to design the most effective LNP is a fundamental challenge.

Now, in a study featured on the cover of the journal Nano Letters, researchers from the University of Pennsylvania’s School of Engineering and Applied Science and Perelman School of Medicine have now shown how to computationally optimize the design of these delivery vehicles.

Using an established methodology for comparing a wide range of variables known as “orthogonal design of experiments,” the researchers simultaneously tested 256 candidate LNPs. They found the frontrunner was three times better at delivering mRNA sequences into T cells than the current standard LNP formulation for mRNA delivery.

The study was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering in Penn’s School of Engineering and Applied Science, and Margaret Billingsley, a graduate student in his lab.

Read the full story in Penn Engineering Today.

February 11, 2022

Newly Discovered ‘Encrypted Peptides’ Found in Human Plasma Exhibit Antibiotic Properties

by Melissa Pappas

The antimicrobial peptides the researchers studied are “encrypted” in that they are contained within Apolipoprotein B, a blood plasma protein that is not directly involved in the immune response, but are not normally expressed on their own.

The rise of drug-resistant bacteria infections is one of the world’s most severe global health issues, estimated to cause 10 million deaths annually by the year 2050. Some of the most virulent and antibiotic-resistant bacterial pathogens are the leading cause of life-threatening, hospital-acquired infections, particularly dangerous for immunocompromised and critically ill patients. Traditional and continual synthesis of antibiotics will simply not be able to keep up with bacteria evolution.

To avoid the continual process of synthesizing new antibiotics to target bacteria as they evolve, Penn Engineers have looked at a new, natural resource for antibiotic molecules.

A recent study on the search for encrypted peptides with antimicrobial properties in the human proteome has located naturally occurring antibiotics within our own bodies. By using an algorithm to pinpoint specific sequences in our protein code, a team of Penn researchers along with collaborators, led by César de la Fuente, Presidential Assistant Professor in Psychiatry, Bioengineering, Microbiology, and Chemical and Biomolecular Engineering, and Marcelo Torres, a post doc in de la Fuente’s lab, were able to locate novel peptides, or amino acid chains, that when cleaved, indicated their potential to fend off harmful bacteria.

Now, in a new study published in ACS Nano, the team along with Angela Cesaro, the lead author and post doc in de la Fuente’s lab, have identified three distinct antimicrobial peptides derived from a protein in human plasma and demonstrate their abilities in mouse models. Angela Cesaro performed a great part of the activities during her PhD under the supervision of corresponding author, Professor Angela Arciello, from the University of Naples Federico II. The collaborative study also includes Utrecht University in the Netherlands.

“We identified the cardiovascular system as a hot spot for potential antimicrobials using an algorithmic approach,” says de la Fuente. “Then we looked closer at a specific protein in the plasma.”

Read the full story in Penn Engineering Today.

February 10, 2022

A New Way to Profile T Cells Can Aid in Personalized Immunotherapy

by Melissa Pappas

A scanning electron micrograph of a healthy human T cell. A better understanding the wide variety of antigen receptors that appear on the surfaces of these critical components of the immune system is necessary for improving a new class of therapies. (Credit: NIAID)

Our bodies are equipped with specialized white blood cells that protect us from foreign invaders, such as viruses and bacteria. These T cells identify threats using antigen receptors, proteins expressed on the surface of individual T cells that recognize specific amino acid sequences found in or on those invaders. Once a T cell’s antigen receptors bind to the corresponding antigen, it can directly kill infected cells or call for backup from the rest of the immune system.

We have hundreds of billions of T cells, each with unique receptors that recognize unique antigens, so profiling this T cell antigen specificity is essential in our understanding of the immune response. It is especially critical in developing targeted immunotherapies, which equip T cells with custom antigen receptors that recognize threats they would otherwise miss, such as the body’s own mutated cancer cells.

Jenny Jiang, Peter and Geri Skirkanich Associate Professor of Innovation in Bioengineering, along with lab members and colleagues at the University of Texas, Austin, recently published a study in Nature Immunology that describes their technology, which simultaneously provides information in four dimensions of T cell profiling. Ke-Yue Ma and Yu-Wan Guo, a former post doc and current graduate student in Jiang’s Penn Engineering lab, respectively, also contributed to this study.

This technology, called TetTCR-SeqHD, is the first to provide such detailed information about single T cells in a high-throughput manner, opening doors for personalized immune diagnostics and immunotherapy development.

There are many pieces of information needed to comprehensively understand the immune response of T cells, and gathering all of these measurements simultaneously has been a challenge in the field. Comprehensive profiling of T cells includes sequencing the antigen receptors, understanding how specific those receptors are in their recognition of invading antigens, and understanding T cell gene and protein expression. Current technologies only screen for one or two of these dimensions due to various constraints.

“Current technologies that measure T cell immune response all have limitations,” says Jiang. “Those that use cultured or engineered T cells cannot tell us about their original phenotype, because once you take a cell out of the body to culture, its gene and protein expression will change. The technologies that address T cell and antigen sequencing with mass spectrometry damage genetic information of the sample. And current technologies that do provide information on antigen specificity use a very expensive binding ligand that can cost more than a thousand dollars per antigen, so it is not feasible if we want to look at hundreds of antigens. There is clearly room for advancement here.”

The TetTCR-SeqHD technology combines Jiang’s previously developed T cell receptor sequencing tool, TetTCR-Seq, described in a Nature Biotechnology paper published in 2018, with the new ability of characterizing both gene and protein expression.

Read the full story in Penn Engineering Today.

February 9, 2022February 9, 2022

Michael Mitchell Receives the 2022 SFB Young Investigator Award

by Ebonee Johnson

Michael Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, has been awarded the 2022 Society for Biomaterials (SFB) Young Investigator Award for his “outstanding achievements in the field of biomaterials research.”

The Society for Biomaterials is a multidisciplinary society of academic, healthcare, governmental and business professionals dedicated to promoting advancements in all aspects of biomaterial science, education and professional standards to enhance human health and quality of life.

Mitchell, whose research lies at the interface of biomaterials science, drug delivery, and cellular and molecular bioengineering to fundamentally understand and therapeutically target biological barriers, is specifically being recognized for his development of the first nanoparticle RNAi therapy to treat multiple myeloma, an incurable hematologic cancer that colonizes in bone marrow.

“Before this, no one in the drug delivery field has developed an effective gene delivery system to target bone marrow,” said United States National Medal of Science recipient Robert S. Langer in Mitchell’s award citation. “Mike is a standout young investigator and leader that intimately understands the importance of research and collaboration at the interface of nanotechnology and medicine.”

Academic recipients of the SFB Young Investigator Award should not exceed the rank of Assistant Professor and must not be tenured at the time of nomination. The award includes a $1,000 endowment.

This story originally appeared in Penn Engineering Today.

February 8, 2022

A Protein Controlled by both Light and Temperature May Open Doors to Understanding Disease-related Cell Signal Pathways

by Melissa Pappas

The brighter edges of the cells in the middle and upper right panels show the optogenetic proteins collecting at the membrane after light exposure. At higher temperatures, however, the proteins become rapidly inactivated and thus do not stay at the membrane, resulting in the duller edges seen in the bottom right panel.

Most organisms have proteins that react to light. Even creatures that don’t have eyes or other visual organs use these proteins to regulate many cellular processes, such as transcription, translation, cell growth and cell survival.

The field of optogenetics relies on such proteins to better understand and manipulate these processes. Using lasers and genetically engineered versions of these naturally occurring proteins, known as probes, researchers can precisely activate and deactivate a variety of cellular pathways, just like flipping a switch.

Now, Penn Engineering researchers have described a new type of optogenetic protein that can be controlled not only by light, but also by temperature, allowing for a higher degree of control in the manipulation of cellular pathways. The research will open new horizons for both basic science and translational research.

Lukasz Bugaj, Assistant Professor in Bioengineering (BE), Bomyi Lim, Assistant Professor in Chemical and Biomolecular Engineering, Brian Chow, Associate Professor in BE, and graduate students William Benman in Bugaj’s lab, Hao Deng in Lim’s lab, and Erin Berlew and Ivan Kuznetsov in Chow’s lab, published their study in Nature Chemical Biology. Arndt Siekmann, Associate Professor of Cell and Developmental Biology at the Perelman School of Medicine, and Caitlyn Parker, a research technician in his lab, also contributed to this research.

The team’s original aim was to develop a single-component probe that would be able to manipulate specific cellular pathways more efficiently. The model for their probe was a protein called BcLOV4, and through further investigation of this protein’s function, they made a fortuitous discovery: that the protein is controlled by both light and temperature.

Read more in Penn Engineering Today.

February 2, 2022

Daniel A. Hammer Named Director of Center for Precision Engineering for Health

by Evan Lerner

Earlier this year, Penn President Amy Gutmann and Vijay Kumar, Nemirovsky Family Dean of Penn’s School of Engineering and Applied Science, announced a $100 m illion commitment to accelerate innovations in medical technologies. Called the Center for Precision Engineering for Health (CPE4H), the initiative aims to bring together researchers from a wide range of fields to develop customizable biomaterials and implantable devices that can be tailored for individualized diagnostics, treatments and therapies.

Now, Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Penn Engineering’s Departments of Bioengineering and Chemical and Biomolecular Engineering, has been named CPE4H’s inaugural director.

“Penn is a unique environment where innovations in healthcare can emerge very rapidly, as we’ve seen with the development of CAR-T cancer immunotherapy, and the design and delivery of mRNA vaccines,” Hammer says. “Engineering plays a central role in making those technologies functional and maximizing their impact, and CPE4H is a golden opportunity to take these technologies to the next level in a way that actually helps people.”

Read the full story in Penn Engineering Today.