Tag: stem cells

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Estelle Sunghee Park Appointed Assistant Professor at Purdue University

Estelle Park, Ph.D.

Penn Bioengineering is proud to congratulate Sunghee Estelle Park, Ph.D. on her appointment as Assistant Professor in the Weldon School of Biomedical Engineering at Purdue University. Park earned her Ph.D. at Penn Bioengineering, graduating in July 2023. She conducted doctoral research in the BIOLines Lab of Dan Huh, Associate Professor in Bioengineering. Her appointment at Purdue will begin January 2024.

During her Ph.D. research, Park forged a unique path that combined principles in developmental biology, stem cell biology, organoids, and organ-on-a-chip technology to develop innovative in vitro models that can faithfully replicate the pathophysiology of various human diseases. Using a microengineered model of the human retina, she discovered previously unknown roles of the MAPK, IL-17, PI3K-AKT, and TGF-β signaling pathways in the pathogenesis of age-related macular degeneration (AMD), presenting novel therapeutic targets that could be further investigated for the development of AMD treatments. More recently, she tackled a significant challenge in the organoid field, the limited tissue growth and maturity in conventional organoid cultures, by designing microengineered systems that enabled organoids to grow with unprecedented levels of maturity and human-relevance. By integrating these platforms with bioinformatics and computational analyses, she identified novel disease-specific biomarkers of inflammatory bowel disease (IBD) and intestinal fibrosis, including previously unknown link between the presence of lncRNA and the development of IBD.

“The unique interdisciplinary expertise I gained from these projects has shaped me into a scholar with a strong collaborative ethos, a quality I hold in high esteem as we work towards advancing our knowledge and management of health and disease,” says Park.

Her vision as an independent researcher is to become a leading faculty who makes impactful contributions to our fundamental understanding of the factors influencing the structural and functional changes of human organs in health and disease. To achieve this, she plans to lead a stem cell bioengineering laboratory with a primary focus on tissue engineering and regenerative medicine. This will involve developing human organoids-on-a-chip systems and establishing next-generation biomedical devices and therapies tailored for regenerative and personalized medicine.

“I am grateful to all my Ph.D. mentors and lab mates at the BIOLines lab and especially my advisor Dr. Dan Huh, for his exceptional guidance, unwavering support, and invaluable mentorship throughout my Ph.D. journey,” says Park. “Dan’s expertise, dedication, and commitment to excellence have been instrumental in shaping both my research and professional development, while also training me to become an independent scientist and mentor.”

Congratulations to Dr. Park from everyone at Penn Bioengineering!

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New Single Cell Analysis Tool

by Nathi Magubane

Researchers at Penn and colleagues have developed a tool to analyze single cells that assesses both the patterns of gene activation within a cell and which sibling cells shared a common progenitor.

3D illustration of a cell held by a pipet and a needle
Arjun Raj of the School of Engineering and Applied Science and the Perelman School of Medicine, former postdoc Lee Richman, now of Brigham and Women’s Hospital, and colleagues have developed a new analysis tool that combines a cell’s unique gene expression data with information about the cell’s origins. The method can be applied to identify new cell subsets throughout development and better understand drug resistance.

Recent advances in analyzing data at the single-cell level have helped biologists make great strides in uncovering new information about cells and their behaviors. One commonly used approach, known as clustering, allows scientists to group cells based on characteristics such as the unique patterns of active or inactive genes or by the progeny of duplicating cells, known as clones, over several generations.

Although single-cell clustering has led to many significant findings, for example, new cancer cell subsets or the way immature stem cells mature into “specialized” cells, researchers to this point had not been able to marry what they knew about gene-activation patterns with what they knew about clone lineages.

Now, research published in Cell Genomics led by University of Pennsylvania professor of bioengineering Arjun Raj has resulted in the development of ClonoCluster, an open-source tool that combines unique patterns of gene activation with clonal information. This produces hybrid cluster data that can quickly identify new cellular traits; that can then be used to better understand resistance to some cancer therapies.

“Before, these were independent modalities, where you would cluster the cells that express the same genes in one lot and cluster the others that share a common ancestor in another,” says Lee Richman, first paper author and a former postdoc in the Raj lab who is now at Brigham and Women’s Hospital in Boston. “What’s exciting is that this tool allows you to draw new lines around your clusters and explore their properties, which could help us identify new cell types, functions, and molecular pathways.”

Researchers in the Raj Lab use a technique known as barcoding to assign labels to cells they are interested in studying, particularly useful for tracking cells, clustering data based on cells’ offspring, and following lineages over time. Believing they could parse more valuable information out of this data by incorporating the cell’s unique patterns of gene activation, the researchers applied ClonoCluster to six experimental datasets that used barcoding to track dividing cells’ offspring. Specifically, they looked at the development of chemotherapy resistance and of stem cells into specialized tissue types.

Read the full story in Penn Today.

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Spencer Haws Receives Druckenmiller Fellowship

Spencer Haws, Ph.D.

Spencer Haws, Postdoctoral Research Fellow in the laboratory of Jennifer E. Phillips-Cremins, Associate Professor and Dean’s Faculty Fellow in Bioengineering and in Genetics, was awarded a 2022 Druckenmiller Fellowship from the New York Stem Cell Foundation Research Institute (NYSCF). This prestigious program is the largest dedicated stem cell fellowship program in the world and was developed to train and support young scientists working on groundbreaking research in the field of stem cell research. Haws is one of only five inductees into the 2022 class of fellows.

Haws earned his Ph.D. in Nutritional Sciences in 2021 from the University of Wisconsin-Madison, where he studied metabolism-chromatin connections under the mentorship of John Denu, Professor in Biomolecular Chemistry at the University of Wisconsin-Madison. As a NYSCF – Druckenmiller Fellow in the Cremins Laboratory for Genome Architecture and Spatial Neurobiology, Haws is using this previously developed expertise to frame his investigations into the underlying mechanisms driving the neurodegenerative disorder fragile X syndrome (FXS). “Ultimately, I hope that this work will help guide the development of future FXS-specific therapeutics of which none currently exist,” says Haws.

Read the full list of 2022 Druckenmiller Fellows and view introductory videos on the NYSCF website.

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

Jennifer Phillips-Cremins, Ph.D.

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.

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Nerve Repair, With Help From Stem Cells

A cross-disciplinary Penn team is pioneering a new approach to peripheral nerve repair.

In a new publication in the journal npj Regenerative Medicine, a team of Penn researchers from the School of Dental Medicine and the Perelman School of Medicine “coaxed human gingiva-derived mesenchymal stem cells (GMSCs) to grow Schwann-like cells, the pro-regenerative cells of the peripheral nervous system that make myelin and neural growth factors,” addressing the need for regrowing functional nerves involving commercially-available scaffolds to guide nerve growth. The study was led by Anh Le, Chair and Norman Vine Endowed Professor of Oral Rehabilitation in the Department of Oral and Maxillofacial Surgery/Pharmacology at the University of Pennsylvania School of Dental Medicine, and was co-authored by D. Kacy Cullen, Associate Professor in Neurosurgery at the Perelman School of Medicine at Penn and the Philadelphia Veterans Affairs Medical Center and member of the Bioengineering Graduate Group:

D. Kacy Cullen (Image: Eric Sucar)

“To get host Schwann cells all throughout a bioscaffold, you’re basically approximating natural nerve repair,” Cullen says. Indeed, when Le and Cullen’s groups collaborated to implant these grafts into rodents with a facial nerve injury and then tested the results, they saw evidence of a functional repair. The animals had less facial droop than those that received an “empty” graft and nerve conduction was restored. The implanted stem cells also survived in the animals for months following the transplant.

“The animals that received nerve conduits laden with the infused cells had a performance that matched the group that received an autograft for their repair,” he says. “When you’re able to match the performance of the gold-standard procedure without a second surgery to acquire the autograft, that is definitely a technology to pursue further.”

Read the full story and view the full list of collaborators in Penn Today.

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Grace Hopper Distinguished Lecture: “Biomanufacturing Vascularized Organoids and Functional Human Tissues” (Jennifer A. Lewis)

We hope you will join us for the 2021 Grace Hopper Distinguished Lecture by Dr. Jennifer Lewis, presented by the Department of Bioengineering. For event links, email ksas@seas.upenn.edu.

Date: Thursday, March 25, 2021
Time: 3:00-4:00 PM EDT

Jennifer A. Lewis

Speaker: Jennifer A. Lewis, Sc.D.
Wyss Professor for Biologically Inspired Engineering
The Wyss Institue
Paulson School of Engineering and Applied Sciences
Harvard University

Title: “Biomanufacturing Vascularized Organoids and Functional Human Tissue”

Following the lecture, join us for a panel discussion “Horizon 2030: Engineering Life & Life in (Bio)Engineering” featuring Dr. Lewis and Penn faculty and moderated by Bioengineering students. Further details here.

Lecture Abstract:
Recent protocols in developmental biology are unlocking the potential for stem cells to undergo differentiation and self-assembly to form “mini-organs”, known as organoids. To bridge the gap from organoid building blocks (OBBs) to therapeutic functional tissues, integrative approaches that combine bottom-up organoid assembly with top-down bioprinting are needed. While it is difficult, if not impossible, to imagine how either organoids or bioprinting alone would fully replicate the complex multiscale features required for organ-specific function – their combination may provide an enabling foundation for de novo tissue manufacturing. My talk will begin by describing our recent efforts to generate organoids in vitro with perfusable microvascular networks that support their viability and maturation. Next, I will describe the generation of 3D vascularized organ-specific tissues by assembling OBBs into a living matrix that supports the embedded printing of macro-vessels by a process known as sacrificial writing in functional tissue (SWIFT).  Though broadly applicable, I will highlight our recent work on kidney, cerebral, and cardiac tissue engineering.

Dr. Lewis Bio:

Jennifer A. Lewis is the Jianming Yu Professor of Arts and Sciences, the Wyss Professor for Biologically Inspired Engineering in the Paulson School of Engineering and Applied Sciences, and a core faculty member of the Wyss Institute at Harvard University. Her research focuses on 3D printing of functional, structural, and biological materials that emulate natural systems. Prior to joining Harvard, Lewis was a faculty member in the Materials Science and Engineering Department at the University of Illinois at Urbana-Champaign, where she served as the Director of the Materials Research Laboratory. Currently, she directs the Harvard Materials Research Science and Engineering Center (MRSEC) and serves the NSF Mathematical and Physical Sciences Advisory Committee.

Lewis has received numerous awards, including the Presidential Faculty Fellow Award, the American Chemical Society Langmuir Lecture Award, the Materials Research Society Medal Award, the American Ceramic Society Sosman and Roy Lecture Awards, and the Lush Science Prize. She is an elected member of the National Academy of Sciences, National Academy of Engineering, National Academy of Inventors, and the American Academy of Arts and Sciences. Her research has enjoyed broad coverage in the popular media. To date, she has co-founded two companies, Voxel8 Inc. and Electroninks, that are commercializing technology from her lab.

Information on the Grace Hopper Lecture:
In support of its educational mission of promoting the role of all engineers in society, the School of Engineering and Applied Science presents the Grace Hopper Lecture Series. This series is intended to serve the dual purpose of recognizing successful women in engineering and of inspiring students to achieve at the highest level.
Rear Admiral Grace Hopper was a mathematician, computer scientist, systems designer and the inventor of the compiler. Her outstanding contributions to computer science benefited academia, industry and the military. In 1928 she graduated from Vassar College with a B.A. in mathematics and physics and joined the Vassar faculty. While an instructor, she continued her studies in mathematics at Yale University where she earned an M.A. in 1930 and a Ph.D. in 1934. Grace Hopper is known worldwide for her work with the first large-scale digital computer, the Navy’s Mark I. In 1949 she joined Philadelphia’s Eckert-Mauchly, founded by the builders of ENIAC, which was building UNIVAC I. Her work on compilers and on making machines understand ordinary language instructions lead ultimately to the development of the business language, COBOL. Grace Hopper served on the faculty of the Moore School for 15 years, and in 1974 received an honorary degree from the University. In support of the accomplishments of women in engineering, each department within the School invites a prominent speaker for a one or two-day visit that incorporates a public lecture, various mini-talks and opportunities to interact with undergraduate and graduate students and faculty.

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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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BE Seminar Series: March 5th with Tara L. Deans, Ph.D.

Our next Penn Bioengineering seminar will be held this Thursday. We hope to see you there!

Speaker: Tara L. Deans, Ph.D.
Assistant Professor
Biomedical Engineering
University of Utah

Date: Thursday, March 5, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building

Title: “Engineering Stem Cells to Create Novel Delivery Vehicles”

 

Abstract:

Synthetic biology has transformed how cells can be reprogrammed, providing a means to reliably and predictably control cell behavior with the assembly of genetic parts into more complex gene circuits. Using approaches and tools in synthetic biology, we are programming stem cells with novel genetic tools to control genes and pathways that result in changes in stem cell fate decisions, in addition to reprogramming terminally differentiated cells to function as unique therapeutic diagnostic and delivery vehicles.

Bio:

Dr. Tara Deans received her PhD from Boston University in Biomedical Engineering. Following her postdoctoral training at Johns Hopkins University, she became an Assistant Professor in Biomedical Engineering at the University of Utah. Currently, Dr. Deans runs an applied mammalian synthetic biology laboratory where her lab focuses on building novel genetic tools to study the mechanisms of stem cell differentiation for the purpose of directing cell fate decisions. Recently, Dr. Deans received four prestigious awards to support this area of research: the NSF CAREER Award, the Office of Naval Research (ONR) Young Investigator Award, the NIH Trailblazer Award and an NIH Director’s New Innovator Award. In addition to her research, Dr. Deans was recently named a STEM Ambassador in the STEM Ambassador Program (STEMAP) at the University of Utah to engage underrepresented groups in STEM fields.

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Replicating fetal bone growth process could help heal large bone defects

Joel Boerckel, Ph.D, Assistant Professor of Orthopaedic Surgery and Bioengineering

To treat large gaps in long bones, like the femur, which result from bone tumor removal or a shattering trauma, researchers at Penn Medicine and the University of Illinois at Chicago developed a process that partially recreates the bone growth process that occurs before birth. A bone defect of more than two centimeters is considered substantial, and current successful healing rates stand at 50% or less, with failure often resulting in amputation. The team hopes that their method, which they’ve developed in rodent models to mimic the process of rapid fetal bone growth, can substantially improve success rates. Their findings are published in Science Translational Medicine. 

Watercolor- A watercolor image depicting the embryonic bone development process, endochondral ossification, featuring cartilage and bone. Credit: Joel Boerckel

“When bones are originally formed in the embryo, they’re first generated from cartilage, like a template,” says senior author Joel Boerckel, an assistant professor of orthopaedic surgery and bioengineering. “In order to regenerate bone within defects that otherwise won’t heal in grown people, we are seeking to recreate the embryonic bone development process.”

To do that, the researchers’ process begins with the delivery of specially engineered stem cells (called a condensation of mesenchymal cells) to the rodents’ bone defect, which sparks endochondral ossification, the specific term for embryonic bone development.

Read more at Penn Medicine News.

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Week in BioE (May 31, 2019)

by Sophie Burkholder

Vector Flow Imaging Helps Visualize Blood Flow in Pediatric Hearts

A group of biomedical engineers at the University of Arkansas used a new ultrasound-based imaging technique called vector flow imaging to help improve the diagnosis of congenital heart disease in pediatric patients. The study, led by associate professor of biomedical engineering Morten Jensen, Ph.D., collaborated with cardiologists at the local Children’s Hospital in Little Rock to produce images of the heart in infants to help potentially diagnose congenital heart defects. Though the use of vector flow imaging has yet to be developed for adult patients, this type of imaging could possibly provide more detail about the direction of blood flow through the heart than traditional techniques like echocardiography do. In the future, the use of both techniques could provide information about both the causes and larger effects of heart defects in patients.

Using Stem Cells to Improve Fertility in Leukemia Survivors

One of the more common side effects of leukemia treatment in female patients is infertility, but researchers at the University of Michigan want to change that. Led by associate professor of biomedical engineering Ariella Shikanov, Ph.D., researchers in her lab found ways of increasing ovarian follicle productivity in mice, which directly relates to the development of mature eggs. The project involves the use of adipose-derived stem cells, that can be found in human fat tissue, to surround the follicles in an ovary-like, three-dimensional scaffold.  Because the radiation treatments for leukemia and some other cancers are harmful to follicles, increasing their survival rate with this stem cell method could reduce the rate of infertility in patients undergoing these treatments. Furthermore, this new approach is innovative in its use of a three-dimensional scaffold as opposed to a two-dimensional one, as it stimulates follicle growth in all directions and thus helps to increase the follicle survival rate.

Penn Engineers Look at How Stretching & Alignment of Collagen Fibers Help Cancer Cells Spread

Cancer has such a massive impact on people’s lives that it might be easy to forget that the disease originates at the cellular level. To spread and cause significant damage, individual cancer cells must navigate the fibrous extracellular environment that cells live in, an environment that Penn Engineer Vivek Shenoy has been investigating for years.

Shenoy is the Eduardo D. Glandt President’s Distinguished Professor with appointments in Materials Science and Engineering, Mechanical Engineering and Applied Mechanics, and Bioengineering. He is also the Director of the Center for Engineering MechanoBiology (CEMB), one of the NSF’s twelve Science and Technology Centers.

Shenoy’s most recent study on cancer’s mechanical environment was led by a postdoctoral researcher in his lab, Ehsan Ban. Paul Janmey, professor in Physiology and Bioengineering, and colleagues at Stanford University also contributed to the study. Shenoy also received the Heilmeier Award this March and delivered the Heilmeier Award Lecture in April.

Read the rest of this story on Penn Engineering’s Medium Blog.

Controlled Electrical Stimulation Can Prevent Joint Replacement Infections

Joint replacements are one of the most common kinds of surgery today, but they still require intense post-operative therapy and have a risk of infection from the replacement implant. These infections are usually due to the inflammatory response that the body has to any foreign object, and can become serious and life-threatening if left untreated. Researchers at the University of Buffalo Jacobs School of Medicine and Biomedical Sciences hope to offer a solution to preventing infections through the use of controlled electrical stimulation. Led by Mark Ehrensberger, Ph.D., Kenneth A. Krackow, M.D., and Anthony A. Campagnari, Ph.D., the treatment system uses the electrical signal to create an antibacterial environment at the interface of the body and the implant. While the signal does not prevent infections completely, these antibacterial properties will prevent infections from worsening to a more serious level. Patented as the Biofilm Disruption Device TM, the final product uses two electrode skin patches and a minimally invasive probe that delivers the electrical signal directly to the joint-body interface. The researchers behind the design hope that it can help create a more standard way of effectively treating joint replacement infections.

People and Places

TBx: Gabriel Koo, Ethan Zhao, Daphne Cheung, and Shelly Teng

For their senior design project, four bioengineering seniors — Gabriel Koo, Ethan Zhao, Daphne Cheung, and Shelly Teng — created a low-cost tuberculosis diagnostic that they called TBx. Using their knowledge of the photoacoustic effect of certain dyes, the platform the group created can detect the presence of lipoarabinomannan in patient urine. The four seniors presented TBx at the Rice360 Design Competition in Houston, Texas this spring, which annually features student-designed low-cost global health technologies.