![\"Image](\"https:\/\/engineering.jhu.edu\/magazine-archive\/wp-content\/uploads\/2023\/12\/innovationcrossroads-spread.jpg\")
\n <\/p>\n\n
Biomedical engineer Jennifer Elisseeff is known for asking bold questions and pursuing seemingly \u201coutlandish\u201d ideas that pay off big. Her latest cross-disciplinary pursuit? Unlocking the mysteries of aging.<\/strong><\/p>\n Senescent cells are known to accumulate in our bodies as we get older. Though they have stopped multiplying, they remain alive, releasing chemicals that can cause inflammation.<\/p>\n Jennifer Elisseeff<\/a> believes these cells might hold the key to unlocking a crucial component of the aging process. To find out how, she is looking to an unlikely culprit: fibroids. Largely benign, these muscular tumors grow in the uterus and cause pain and bleeding. Fibroids are packed with senescent cells.<\/p>\n \u201cIf you can understand what\u2019s going wrong, you can start blocking it,\u201d says Elisseeff, who is collaborating with researchers in the Department of Gynecology and Obstetrics at Johns Hopkins Medicine.<\/p>\n The project\u2014one in a series of multidisciplinary efforts meant to chip away at the mechanisms of aging and find therapies to help our bodies regenerate\u2014is emblematic of Elisseeff\u2019s penchant to ask bold questions and forge collaborations across a disparate array of fields.<\/p>\n A biomedical engineering professor at Johns Hopkins for 22 years, Elisseeff was recently named interim director of the Department of Chemical and Biomolecular Engineering<\/a>. She is also the Morton Goldberg Professor of Ophthalmology.<\/p>\n Notably, she is the university\u2019s only faculty member to be elected to all three national academies: the National Academy of Sciences (2023), the National Academy of Engineering (2018), and the National Academy of Medicine (2018). After first using her biomaterials expertise to develop regenerative therapies and launch two successful startup companies, Elisseeff took a rare mid-career pivot into a complex field outside her specialty: immunology.<\/p>\n Today she is a leading expert on regenerative immunology\u2014a burgeoning area of research that aims to harness the power of the immune system to heal the body\u2014and her innovative collaborations with experts in cancer immunotherapy and computational biology, among other fields, have wide-ranging implications for tissue regeneration, cancer therapies, and diseases of aging.<\/p>\n \u201cJennifer is not afraid to come up with an idea that could very well be looked at as outlandish,\u201d says Drew Pardoll, director of the Bloomberg- Kimmel Institute for Cancer Immunotherapy and oncology professor at Johns Hopkins Medicine. \u201cSome of those ideas develop momentum and, all of a sudden, outlandish becomes transformative.\u201d<\/p><\/blockquote>\n Elisseeff has been working on senescent cells for more than six years. In a seminal paper published in 2017 in Nature Medicine<\/em><\/a>, she showed that eliminating senescent cells from an arthritic joint reduced pain and increased cartilage development. Her lab is now part of the NIH Common Fund Cellular Senescence Network, a collaborative program uniting cellular senescence researchers to study and publish public data on these important cells.<\/p>\n Her interest in senescent cells grew out of her fascination with the immune system. Senescent cells signal that the immune system has been activated, which occurs during tissue development and repair, as well as during harmful chronic inflammation.<\/p>\n She explains that while we most often think about the immune system in the context of vaccine efficiency or fighting infections, part of its job is to recycle cells that are no longer functioning as they should. The immune system also plays a role in the aging process. \u201cThe immune system is a first responder to tissue damage,\u201d Elisseeff says, which has led her to ask: \u201cHow does aging change the immune environment and impact our ability to repair tissues?\u201d<\/p>\n In partnership with bioinformatics colleagues at Johns Hopkins Medicine, Elisseeff has developed computational techniques to study how the immune system communicates\u2014in young animals versus older animals\u2014and how it changes and inhibits tissue repair. The goal, she says, is a new strategy for developing therapeutic targets for the illnesses of aging, such as neurodegenerative disease and frailty. This new strategy, she explains, will need to consider immune factors, such as diet, microbiome, history of infections, and comorbidities.<\/p>\n \u201c[Typically] those factors aren\u2019t part of the design process when you\u2019re making new therapies for people,\u201d she says. \u201cHow many therapies failed because those factors weren\u2019t considered?\u201d Elisseeff was the first engineer to collaborate with the Bloomberg-Kimmel Institute for Cancer Immunotherapy, and she has since recruited other biomedical engineers to join her efforts there. \u201cHopkins has amazing immunologists,\u201d she says, \u201cand not only basic science immunology, but also translational immunology, which is super exciting.\u201d<\/p>\n Her current focus involves leading the institute\u2019s program to engineer the tumor microenvironment, the complex ecosystem of cells, blood vessels, and other components that surround a tumor. She found that senescent cells play a role in these tumor microenvironments: When noncancer cells in a tumor were senescing, they could give the tumor a \u201csenescence signature\u201d that correlated with poor immunotherapy outcomes for cancer patients.<\/p>\n \u201cShe\u2019s connecting dots that no other scientist has connected,\u201d Pardoll says. \u201cThis is really very novel.\u201d<\/p>\n Elisseeff\u2019s senescence work has helped the researchers at the Bloomberg-Kimmel Institute to draw a clearer picture of the tumor microenvironment. \u201cIt had a major impact on our research into how a tumor microenvironment is organized, which, in turn, has broadened our thinking about how to therapeutically target these cells,\u201d says Pardoll.<\/p>\n As Elisseeff learns more about senescent cells, and the other cells within tumors, she is aiming to engineer the ideal tumor microenvironment to make cancer immunotherapy treatments more effective\u2014and make tumors more susceptible to those treatments.<\/p>\n \u201cWhat environment promotes tumor growth and more resistance to therapies,\u201d she says, \u201cversus inhibiting tumor growth and increasing immunotherapy response?\u201d<\/p>\n When Elisseeff was a high schooler in the early 1990s, she could frequently be found in her father\u2019s laboratory in the Department of Ocean and Mechanical Engineering at Florida Atlantic University in Boca Raton. A lover of nature with a penchant for science fairs, she was soon conducting her own basic research. In one particularly prescient example, the young Elisseeff studied how microbes impacted the chemical process on metal surfaces.<\/p>\n Even from a young age, she was intrigued by the collision of the natural and the synthetic. \u201cInnovation happens at the crossroads,\u201d she says.<\/p>\n On the recommendation of a favorite science teacher, Elisseeff attended Carnegie Mellon University, settling on an undergraduate degree in chemistry. While studying polymer chemistry, Elisseeff was introduced to the idea of combining polymers with biology\u2014that is, biomaterials\u2014 bringing her closer to the medical field. Elisseeff pursued her PhD in biomedical engineering at the Harvard\u2013MIT Division of Health Sciences and Technology, attended two years of medical school, and completed a postdoctoral program at the National Institutes of Health.<\/p>\n She joined Hopkins\u2019 Department of Biomedical Engineering<\/a> in 2001. \u201cWhat is unique about biomedical engineering here is how it\u2019s embedded in medicine,\u201d she says. \u201cI was attracted by the ability to bridge the different schools and start a new collaboration with physicians out of the blue, whether it be a cornea surgeon or a gynecologist studying fibroids or a cancer researcher.\u201d<\/p>\n Her initial focus was engineering biomaterials, synthetic systems that could heal tissue wounds. She developed adhesive and biomaterial technologies to treat arthritis, restoring cartilage that had deteriorated in patients\u2019 aching knees. The work led to her first startup, a company called Cartilix Inc. that was founded in 2004 and acquired by Biomet Inc. five years later. By then, Elisseeff\u2019s interests had expanded into soft tissue regeneration, and she founded two more startups to translate her work.<\/p>\n A proponent of translating academic research into treatments for patients, Elisseeff recruited Jordan Green<\/a>, the Herschel L. Seder Professor in Biomedical Engineering, to help establish the Translational Tissue Engineering Center<\/a> (TTEC), a collaboration with the Wilmer Eye Institute, in 2010.<\/p>\n \u201cJennifer cares about the big picture,\u201d says Green, who is now the department\u2019s vice chair for research and translation and TTEC\u2019s associate director. \u201cIt\u2019s not just the science, but how the science can impact society.\u201d<\/p><\/blockquote>\n Following Elisseeff\u2019s lead, Green became involved in the work of the ophthalmologists at Wilmer\u2014a partnership he hadn\u2019t expected. \u201cShe likes to bring different kinds of people together,\u201d he says, noting that the TTEC floor is often filled with a mix of clinicians, medical students, residents, and researchers working together. \u201cThat environment can more easily lead to translational outcomes.\u201d<\/p>\n Green has since founded two startups: Asclepix Therapeutics, which develops a peptide drug to treat wet age-related macular degeneration, and Cove Therapeutics, which develops nonviral gene therapy in the eye. \u201cIf it wasn\u2019t for Jennifer\u2019s leadership, I don\u2019t think those would have happened,\u201d he says. \u201cIt resonates with me that the research we do can lead to improvement to the quality of life for people who need help.\u201d<\/p>\n It was the process of translating technologies to the clinical setting that made Elisseeff in 2013 begin to take an interest in the immune system \u2014our body\u2019s complex web of defenses\u2014which she until then knew little about.<\/p>\n \u201cWe developed these therapies, but if you put them in an inflammatory environment, they\u2019re not going to work,\u201d she says. Without any formal immunology training, Elisseeff came to the conclusion that the immune system was key to successful regeneration. \u201cThat was a real clincher,\u201d she says. \u201cI had to learn some immunology.\u201d<\/p>\n So, in an exceedingly rare move for an already-renowned researcher a dozen years into her career, Elisseeff embarked on a semesterlong sabbatical at the Swiss Federal Institute of Technology in Lausanne for an intensive immersion into the world of immunology.<\/p>\n When she returned a few months later, Elisseeff connected with Kaitlyn Sadtler, a new graduate student with an interest in immunology who wanted to do a rotation in her lab. \u201cHaving had zero experience in bioengineering, I had no idea how big of a deal she was,\u201d Sadtler says, laughing.<\/p>\n Soon, Sadtler had joined Elisseeff\u2019s lab. Elisseeff, along with Pardoll, advised Sadtler on her PhD thesis. The resulting paper, a transformative work published in Science in 2016, showed that a specific type of T cell, previously known to combat parasitic microbial infections, was also central to wound healing.<\/p>\n Now a tenure-track investigator at the National Institutes of Health and chief of the Section on Immunoengineering, Sadtler says Elisseeff remains the only female principal investigator she has ever worked under. Elisseeff\u2019s example as a role model\u2014she once bought her mentee dinner when the graduate student looked wan after a long day in the lab\u2014inspired Sadtler to mentor other women in science. \u201cIt\u2019s hard to be what you can\u2019t see,\u201d she says.<\/p>\n Elisseeff considers her mentorship of women engineers one of her greatest accomplishments to date. \u201cI\u2019ve trained a lot of [women] students who are now faculty,\u201d she says. \u201cWhen you look at gender diversity in [engineering] departments, there\u2019s usually not a great balance. My contribution of training women who now are in faculty positions around the world doing great work is important for the field.\u201d<\/p>\n Elisseeff\u2019s lab work isn\u2019t her only race against time. She also competes in short-distance triathlons, races that include swimming, biking, and running segments, as part of her personal quest to age healthfully.<\/p>\n \u201cIt\u2019s a sport where you have some diversity of different activities,\u201d she says. \u201cI enjoy mixing it up.\u201d<\/p>\n When she\u2019s not listening to music to stave off the tedium of the long, slow runs mandated by her triathlon training program (\u201cIt\u2019s boring trying to be disciplined to go slower,\u201d she says), Elisseeff sometimes finds herself musing on the engineering problems she\u2019s trying to solve in the lab. Her next \u201ccrazy challenge\u201d stems from her fibrosis work.<\/p>\n Elisseeff\u2019s lab has data to suggest that T cells \u2014adaptive immune cells known to combat outside invaders, such as germs and disease\u2014 might be recognizing fibrosis and perhaps, by extension, other types of tissue damage. If that\u2019s true, it goes against basic immunology dogma because T cells aren\u2019t supposed to be self-reactive: That\u2019s considered an autoimmune disease. The notion is \u201ca little bit controversial in some sense,\u201d Elisseeff says.<\/p>\n \u201cThe adaptive immune system isn\u2019t recognized as having a big role in tissue repair or a lack of repair,\u201d she says. \u201cThis is a new way of looking at the role of the immune system in tissue repair that\u2019s just very different.\u201d But if Elisseeff can prove that T cells are recognizing fibrosis\u2014 which is no small feat\u2014the finding could open up a huge new avenue of research into how T cells contribute to aging.<\/p>\n \u201cI feel like I haven\u2019t made my most important contribution yet,\u201d she says.<\/p>\n","protected":false},"excerpt":{"rendered":" Biomedical engineer Jennifer Elisseeff is known for asking bold questions and pursuing seemingly \u201coutlandish\u201d ideas that pay off big. Her latest cross-disciplinary pursuit? Unlocking the mysteries of aging.<\/p>\n","protected":false},"author":30,"featured_media":19475,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[28],"tags":[],"class_list":["post-19471","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-features","issue-winter-2024"],"acf":[],"yoast_head":"\n![\"Image](\"https:\/\/engineering.jhu.edu\/magazine-archive\/wp-content\/uploads\/2023\/12\/JHMI_9-27-23_0118-300x200.jpeg\")
<\/p>\nThe Immune System\u2019s \u2018First Responder\u2019<\/h2>\n
![\"Image](\"https:\/\/engineering.jhu.edu\/magazine-archive\/wp-content\/uploads\/2023\/12\/JHMI_9-27-23_0224-300x200.jpeg\")
<\/p>\nImproving Lives<\/h2>\n
![\"Image](\"https:\/\/engineering.jhu.edu\/magazine-archive\/wp-content\/uploads\/2023\/12\/JHMI_9-27-23_0393-1024x683.jpeg\")
<\/h2>\nMentoring Women in Science<\/h2>\n
The Next \u2018Crazy Challenge\u2019<\/h2>\n