Breaking the rules to engineer the human immune system
Not to overstate things, but Professor Ankur Singh and his research colleagues at Cornell’s Sibley School of Mechanical and Aerospace Engineering are helping to create a new field. Singh and the members of his Immunotherapy and Cell Engineering Lab (ICEL) want to know everything there is to know about the human immune system and tackle it from an engineering standpoint. Singh’s research group is working on recreating immune organs in the lab outside the body using synthetic materials. Oh, and while they are at it, they want to fully understand how human stem cells work as well.
“Immune engineering is a nascent field and we are aggressively exploring it,” says Singh. “We want to understand the fundamentals of the human immune system, good or bad, and exploit it by creating innovative technologies to treat cancer, infections, and arthritis. I have chosen a very complicated organ and cell system on purpose because there is so much to learn and so much potential good that can come of it.” Singh came to Cornell after postdoctoral work at Georgia Tech. “The structure here makes it easy to collaborate. At Cornell, I find scientists across various engineering disciplines as well as at the Veterinary School who are very receptive to what we do” says Singh. “Also, the faculty and students here are extraordinary. Finest in the world.”
Another area of research where Singh and his colleagues are breaking new ground is stem cell engineering. “Until now, stem cell research has been predominantly seen from biology and biochemistry standpoints. We are taking a mechanical engineering approach to regulate these important cells. We are slowly learning to control the behavior of pluripotent stem cells (that can make any other cell type in your body) using micro-and-nanometer scale engineering platforms.” One of Singh’s stem cell papers was published in Nature Methods in 2013.
“When this position at Cornell opened up, I wanted to apply,” says Singh. “There are few universities you wish to be a part of. Cornell was on top of my list. There is a strong history of academic excellence and culture here.” Singh adds with a smile, “I grew up reading Professor Mike Shuler’s bioprocess engineering book. I never thought I would be discussing my scientific thoughts with him one day.” Singh also likes the ready inclusion of undergraduates in research labs at Cornell. “Undergrads are always a key component of research. We have projects that are just the right size for them. I have been lucky to have several outstanding undergraduates from different engineering disciplines in my lab. ”
While the academic and intellectual setting at Cornell is perfect for Ankur Singh and his research interests, it might surprise the reader to know that, (even though Singh has spent most of his adult life in Mumbai, Texas, and Georgia), the long stretches of cloudy weather in Ithaca are also just right for him. “I have to admit, I like the rainy weather. I am much more functional when the skies are grey.” If Singh is more focused when the weather is cloudy, he should have a long and productive career at Cornell.
Singh is among 13 outstanding U.S. scientists recently recognized as 2014 Young Innovators in Cellular and Molecular Bioengineering. Singh is being recognized for his work in fabricating jello-like artificial tissues using novel biomaterials that allow for independent control of both cell adhesion chemistry and tissue mechanics. This ability to adjust both cell adhesion chemistry and tissue mechanics provides a functional platform for studying cancer and stem cells, screening therapeutics, and gives researchers a new and powerful tool for 3D tissue building.
Singh describes his research as happening “at the interface of biomaterials and human cells. We use micro-nanofabrication as a tool to study signaling, survival, and mechanobiology in immune and stem cells.” One of the goals of Singh’s ICEL group is to create within ten years an artificial immune organ, either in a dish or on a chip. “This would allow other researchers to expand their work considerably,” says Singh. “We want to reach a 90% or 100% cure rate for cancers and infections and artificial immune organs would help make this possible.”
As Singh went deeper into his research, he noticed that many young researchers around the world were interested in approaching biomedical problems by understanding immunology. Singh, taking a leadership role, petitioned the Society for Biomaterials to start a special interest group in Immune Engineering. His request was unanimously approved by the council consisting of leaders in bioengineering and he was elected as the inaugural chair of the Immune Engineering special interest group. The Society is looking forward to its first major Immune Engineering-focused sessions at the 2015 annual conference in North Carolina.
At this early point in his career, Ankur Singh does not yet know everything there is to know about the human immune system, but he is off to a good start. He and his group of students from diverse engineering backgrounds have not yet engineered a “functional” human immune organ, but they are certainly well on their way and predict a breakthrough soon. “Much of the scientific research has relied on what your immune system does by default. We are breaking the rules by engineering the immune system the way we want. I am very excited to be at Cornell and to have the chance to do this work,” says Singh. So now let’s all hope for cloudy skies and more rain.
2015 was a big year for Ankur Singh. His lab took several big steps toward his goal of engineering a functional human immune organ. An article published online June 3 in the journal Biomaterials announced that Singh’s lab had managed to create a functional synthetic immune organ that produces antibodies and can be controlled in the lab. And then in October the same journal, Biomaterials, published a paper showing that Singh’s lab had succeeded in engineering a lymphoma organoid. The organoid is a 3-D tissue culture that mimics the complex environment of lymphomas and allows researchers to gain a deeper understanding of non-Hodgkin lymphoma tumors.
2016 is off to a great start for Singh, as well. His National Science Foundation (NSF) CAREER proposal “Dynamic Living Hydrogel Networks for Spatio-Temporal Control of Cell Signaling” has been approved and funded. In Singh’s words, “This NSF CAREER award will overcome the current bottlenecks in biomaterials research by enabling the development of a new class of hydrogel that dynamically communicates with cells to control their fates. The proposed research will benefit society by developing advanced bio-functional tissues for regenerative medicine. In particular we expect this work to generate dynamic biomaterials for better understanding of stem cells and their interactions with local surroundings that will help treatment of neurological disorders and enable regeneration of neural grafts for short and long nerve gaps. The outcomes of this research will catalyze potential avenues of investigation in multiple disciplines, including cell culture, tissue fabrication, blood vessel generation, drug delivery, tumor engineering, and implants.”