Jenny Jiang Wins CZI Grant to Investigate the Potential Trigger for Neurodegenerative Diseases

Jenny Jiang, Ph.D.

TDP-43 may be one of the most dangerous proteins in the human body, implicated in neurodegenerative conditions like ALS and Alzheimer’s disease. But the protein remains mysterious: how TDP-43 interacts with the immune system, for instance, is still unclear. 

Now, Ning Jenny Jiang, J. Peter and Geri Skirkanich Associate Professor of Innovation in Bioengineering, has been selected for the Collaborative Pairs Pilot Project Awards, sponsored by the Chan Zuckerberg Initiative (CZI), to investigate the relationship between TDP-43 and the immune system. 

Launched in 2018, the Collaborative Pairs Pilot Project Awards support pairs of investigators to explore “innovative, interdisciplinary approaches to address critical challenges in the fields of neurodegenerative disease and fundamental neuroscience.” Professor Jiang will partner with Pietro Fratta, MRC Senior Clinical Fellow and MNDA Lady Edith Wolfson Fellow at the University College London Queen Square Institute of Neurology.

The TDP-43 protein is associated with neurodegenerative diseases affecting the central nervous system, including ALS and Alzehimer’s disease. While the loss of neurons and muscle degeneration cause the progressive symptoms, the diseases themselves may be a previously unidentified trigger for abnormal immune system activity. 

One possible link is the intracellular mislocalization of TDP-43 (known as TDP-43 proteinopathy), when the protein winds up in the wrong location, which the Jiang and Fratta Labs will investigate. Successfully proving this link could result in potentially game-changing new therapies for these neurodegenerative diseases. 

The Jiang Lab at Penn Engineering specializes in systems immunology, using high-throughput sequencing and single-cell and quantitative analysis to understand how the immune system develops and ages, as well as the molecular signatures of immune related diseases. Jiang joined Penn Bioengineering in 2021. 

Since arriving on campus, Jiang has teamed with the recently formed Penn Anti-Cancer Engineering Center (PACE), which seeks to understand the forces that determine how cancer grows and spreads, and Engineers in the Center for Precision Engineering (CPE4H), which focuses on innovations in diagnostics and delivery in the development of customizable biomaterials and implantable devices for individualized care. 

Jiang was elected a member of the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows in 2021, and has previously won multiple prestigious awards including the NSF CAREER, a Cancer Research Institute Lloyd J. Old STAR Award, and a CZI Neurodegeneration Challenge Network Ben Barres Early Career Acceleration Award.

Jiang is a leader in high-throughput and high-dimensional analysis of T cells, a type of white blood cell crucial to the functioning of a healthy immune system. A recent study in Nature Immunology described the Jiang Lab’s TetTCR-SeqHD technology, the first approach to provide a multifaceted analysis of antigen-specific T cells in a high-throughput manner.

The CZI Collaborative Pairs Pilot Project Awards will provide $200,000 of funding over 18 months with a chance to advance to the second phase of $3.2 million in funding over a four-year period. 

Read the full list of grantees on the CZI’s Neurodegeneration Challenge Network (NDCN) Projects website here.

Penn Anti-Cancer Engineering Center Will Delve Into the Disease’s Physical Fundamentals

by Evan Lerner

A colorized microscope image of an osteosarcoma shows how cellular fibers can transfer physical force between neighboring nuclei, influencing genes. The Penn Anti-Cancer Engineering Center will study such forces, looking for mechanisms that could lead to new treatments or preventative therapies.

Advances in cell and molecular technologies are revolutionizing the treatment of cancer, with faster detection, targeted therapies and, in some cases, the ability to permanently retrain a patient’s own immune system to destroy malignant cells.

However, there are fundamental forces and associated challenges that determine how cancer grows and spreads. The pathological genes that give rise to tumors are regulated in part by a cell’s microenvironment, meaning that the physical push and pull of neighboring cells play a role alongside the chemical signals passed within and between them.

The Penn Anti-Cancer Engineering Center (PACE) will bring diverse research groups from the School of Engineering and Applied Science together with labs in the School of Arts & Sciences and the Perelman School of Medicine to understand these physical forces, leveraging their insights to develop new types of treatments and preventative therapies.

Supported by a series of grants from the NIH’s National Cancer Institute, the PACE Center is Penn’s new hub within the Physical Sciences in Oncology Network. It will draw upon Penn’s ecosystem of related research, including faculty members from the Abramson Cancer Center, Center for Targeted Therapeutics and Translational Nanomedicine, Center for Soft and Living Matter, Institute for Regenerative Medicine, Institute for Immunology and Center for Genome Integrity.

Dennis Discher and Ravi Radhakrishnan

The Center’s founding members are Dennis Discher, Robert D. Bent Professor with appointments in the Departments of Chemical and Biomolecular Engineering (CBE), Bioengineering (BE) and Mechanical Engineering and Applied Mechanics (MEAM), and Ravi Radhakrishnan, Professor and chair of BE with an appointment in CBE.

Discher, an expert in mechanobiology and in delivery of cells and nanoparticles to solid tumors, and Radhakrishnan, an expert on modeling physical forces that influence binding events, have long collaborated within the Physical Sciences in Oncology Network. This large network of physical scientists and engineers focuses on cancer mechanisms and develops new tools and trainee opportunities shared across the U.S. and around the world.

Lukasz Bugaj, Alex Hughes, Jenny Jiang, Bomyi Lim, Jennifer Lukes and Vivek Shenoy (Clockwise from upper left).

Additional Engineering faculty with growing efforts in the new Center include Lukasz Bugaj, Alex Hughes and Jenny Jiang (BE), Bomyi Lim (CBE), Jennifer Lukes (MEAM) and Vivek Shenoy (Materials Science and Engineering).

Among the PACE Center’s initial research efforts are studies of the genetic and immune mechanisms associated with whether a tumor is solid or liquid and investigations into how physical stresses influence cell signaling.

Originally posted in Penn Engineering Today.