On this interview from SfN 2024, Professor Nancy Ip, President of The Hong Kong College of Science and Know-how, shares insights into her pioneering neuroscience analysis. She discusses her journey, breakthroughs in neurotrophic components, and revolutionary approaches to Alzheimer’s illness remedy.
Professor Ip highlights immune modulation, mind signaling pathways, and the potential of conventional Chinese language drugs in combating neurodegeneration. She additionally displays on how new applied sciences and precision drugs are shaping the way forward for Alzheimer’s analysis and the significance of lifelong mind well being.
To start out, may you introduce your self and share what drew you to neuroscience? How did your early analysis on neurotrophic components form your strategy to learning mind growth and neurodegenerative illnesses?
I’m Nancy Ip, the Morningside Professor of Life Science and President of The Hong Kong College of Science and Know-how.
My curiosity in neuroscience started throughout graduate college. After incomes my bachelor’s diploma from Simmons Faculty in Boston, I entered graduate college at Harvard Medical College, the place I joined a neuroscience lab, drawn to the complexity and thriller of the mind. At the moment, we knew little or no about this extremely intricate organ, and I used to be particularly desirous to discover how neurons talk.
My thesis work recognized a novel communication mechanism involving peptides similar to VIP and secretin, a major discovering as the one identified neurotransmitters within the mammalian system have been small molecules like acetylcholine. I discovered that these peptides have been utilized relying on the sample of stimulation, and on account of this novel discovery, I used to be the primary creator of a number of high-profile papers.
After finishing my Ph.D., I did a postdoc, then took a yr off earlier than working at Lifecodes, a biotech firm. Whereas I loved the work, I missed neuroscience analysis and realized that was the place my true ardour lay. So, when the possibility arose to affix Regeneron, a promising younger startup targeted on neurodegenerative illnesses, I took it. At Regeneron, I labored on neurotrophic components and contributed to the invention of two neurotrophins (Neurotrophin-3 and Neurotrophin-4) in addition to CNTF (ciliary neurotrophic issue). Our work superior the sector of neurotrophic components, showcasing their position in neural growth and plasticity. Regeneron’s contributions have had a long-lasting impression on neuroscience.
In 1993, I returned to Hong Kong and joined the Hong Kong College of Science and Know-how (HKUST), marking the beginning of my educational profession.
My preliminary educational analysis aimed to know how neurotrophic components and receptor signaling regulate synapses—the junctions the place neurons talk. Later, I shifted focus to the mechanisms underlying synaptic plasticity, which is key to studying and reminiscence. Our staff made vital strides in these areas, paving the way in which to check Alzheimer’s illness (AD), a situation marked by reminiscence loss. Since synapse loss is a key characteristic of AD, I grew to become taken with investigating how dysregulation of neurotrophic components contributes to synapse loss and impaired synaptic perform in AD, which led to deeper, multi-level research of the illness.
Picture Credit score: Juan Gaertner/Shutterstock.com
Your analysis on the immune system’s position in Alzheimer’s illness has been groundbreaking. How do you assume these insights may remodel the way in which we strategy treating this situation?
Uncovering the position of the immune system in AD pathology has considerably enhanced our understanding of AD pathogenesis. Genetic proof exhibiting the affiliation of immune system with AD additional helps the roles of the impaired immune system within the pathogenesis of AD.
With higher understanding of the molecular and mobile biology underlying immune system dysfunction, we’re in a position to determine new molecular targets and develop novel disease-modifying remedy approaches. This information may assist us higher perceive the anticipated outcomes from modulating the corresponding expression/exercise of potential targets in mannequin mice of AD.
Moreover, genetics and biomarker research are enabling us to foretell and reveal the impaired immune system in AD. This data can be utilized to stratify sufferers with impaired immune capabilities. Thus, concentrating on the impaired immune system in AD may very well be used as a precision drugs strategy.
How may your discoveries about mind signaling pathways result in new therapies that enhance cognitive perform for sufferers with Alzheimer’s?
Our work on mind signaling pathways has recognized new molecular targets and its related biology in addition to unveiled new therapeutic approaches.
For instance, in our work on the cytokine IL-33, we discovered that activation of the signaling pathway, by administering IL-33 to AD mannequin mice, decreases amyloid beta (Aβ) pathology and alleviates reminiscence impairment within the mice.
This thrilling discovery highlighted immune modulation as a possible AD remedy and IL-33 as a possible drug goal, resulting in the event of IL-33 modulators as potential therapeutics. Our subsequent research revealed that IL-33 reduces Aβ pathology by mobilizing microglia, a serious immune cell kind within the mind, in the direction of poisonous Aβ to engulf and clear them.
Our examine of the IL33/ST2 pathway additionally led to the invention of a novel remedy strategy. On this examine, human information evaluation revealed that blood ranges of soluble ST2 (sST2), a decoy receptor of IL-33/ST2, will increase in AD sufferers, whereas mouse mannequin evaluation revealed the motion of sST2 on regulating molecular phenotypes and the capabilities of microglia. These insights highlighted sST2 as a promising drug goal for AD, resulting in the event of novel sST2 modulators as potential therapeutics.
The hyperlink between growing old and the immune system is a key focus of your work. How do you assume higher understanding this connection may enhance high quality of life as individuals age?
A greater understanding of this connection, notably how the immune system adjustments with growing age, will present necessary insights on how you can handle age-related illnesses in addition to promote wholesome growing old.
Getting older is the strongest threat issue of AD. As Alzheimer’s researchers, it will be important for us to know the adjustments in particular immune biomarkers as people age and decide whether or not any of them function pathological components or contribute to the pathogenesis of AD. Clearer understanding of how these biomarkers contribute to illness will assist determine promising targets for drug growth.
Information of how the immune system adjustments with age may assist in creating preventive measures. This contains life-style selections to advertise wholesome growing old, in addition to vaccines and dietary supplements that may improve immune perform and scale back the danger of infections and illnesses.
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You’ve been exploring how synaptic connections could be strengthened to fight neurodegenerative illnesses. What broader impression may these findings have on future therapies for memory-related problems?
Regulation of synaptic energy and communication is the fundamental mechanism underlying reminiscence formation and storage.
Thus, by understanding the mechanisms underlying synapse formation and synaptic plasticity, we are able to delineate how deregulation of the method contributes to the pathogenesis of memory-related problems. With improved understanding, we are able to then develop efficient therapies for corresponding memory-related problems.
In your work on drug discovery, together with exploring compounds from conventional Chinese language drugs, what potential do you see for these therapies to handle international healthcare challenges in neurodegeneration?
Our drug discovery work has recognized a number of novel molecular targets and a variety of potential drug candidates with numerous mechanisms of motion. Our exploration of conventional Chinese language drugs (TCM) has additionally recognized compounds or herbs with helpful results in AD.
TCM presents a wealth of promising drug candidates supported by its lengthy historical past of use and intensive scientific information. We’ve got sought to raised perceive the organic actions of the TCM herbs and their energetic compounds by evaluating their mechanisms of motion in scientific mannequin programs.
A number of the potential drug leads my lab has recognized/developed present vital promise in treating AD. These are both in co-development with, or have been licensed for additional growth by, pharmaceutical firms. My lab has additionally pioneered a gene remedy expertise for familial AD, which has been licensed for additional growth.
It must be famous that drug growth is a protracted and arduous course of, and it might be a few years earlier than therapies could be accessible for scientific use.
Drug growth for AD is especially difficult as a result of AD is a fancy, multifactorial situation involving completely different neuropathological mechanisms and a number of physique programs. Growing efficient therapies requires an intensive understanding of illness mechanisms.
Thankfully, in recent times, our understanding of AD and different neurodegenerative illnesses has grown significantly. World large-scale analysis collaborations are unraveling the complexities of those circumstances, which have expanded illness targets for drug growth.
In the meantime, new applied sciences similar to machine studying and synthetic intelligence are streamlining and accelerating the drug growth course of. It is just a matter of time earlier than we now have extra disease-modifying therapies for AD and different neurodegenerative circumstances.
As Alzheimer’s analysis progresses, how may new therapies concentrating on the immune system and mind well being shift the way in which we forestall or handle the illness in the long run?
Historically, a lot of Alzheimer’s drug growth efforts have targeted on the 2 hallmark options of the illness: amyloid plaques and tau tangles. New understanding of the position of the immune system in AD is unveiling new molecular targets and new methods for drug growth, similar to restoring impaired immune perform in AD and addressing neuroinflammation.
This shift in focus will result in the event of recent courses of illness modifying therapies. As an example, therapies may goal particular immune cells or pathways that contribute to neurodegeneration to mitigate the inflammatory processes that exacerbate cognitive decline.
Immune-targeted methods may be used alongside present medicine to offer complete remedy choices that each alleviate signs and modify illness trajectory.
With fast advances in mind science, how do you see new applied sciences shaping the way forward for neuroscience analysis and remedy approaches?
New advances are shaping mind analysis in very thrilling methods. They’re deepening our understanding of the mind in addition to mind illnesses and problems at a fast tempo, and accelerating progress within the growth of recent therapies and therapies. As an example, advances in neuroimaging are offering unprecedented insights into mind exercise and connectivity.
New applied sciences are additionally serving to to disclose the organic adjustments in mind cells at a single-cell degree and inside a spatial context. This development helps us delineate the pathological mechanisms of AD in better element.
Different advances embody revolutionary genetic and molecular instruments similar to CRISPR and different gene-editing applied sciences to control genes linked to neurological problems, which may result in focused therapies for circumstances similar to familial AD.
In the meantime, machine studying and synthetic intelligence are serving to researchers analyze huge quantities of neuroimaging and genetic information, determine patterns, and develop predictive fashions to additional help and speed up analysis efforts.
As you’re employed on the frontlines of neuroscience innovation, what upcoming developments within the discipline do you consider can have the best impression on society?
We’re enthusiastic about a variety of upcoming developments. The primary is early analysis of AD – figuring out sufferers when the illness remains to be in its early stage and treatable.
Presently, AD is primarily recognized by way of cognitive assessments however by the point cognitive decline is clear, the illness has progressed to a complicated stage. Early analysis is a game-changer, permitting for well timed scientific interventions that may result in higher remedy outcomes, thus bettering the standard of life for sufferers.
The second is the flexibility to stratify AD sufferers into illness subtypes for growth of precision drugs approaches. This may assist determine appropriate candidates for focused drug remedy in scientific trials with particular disease-modifying medicine.
With precision drugs, sufferers will obtain tailor-made therapies primarily based on their particular person genetic profiles and illness subtypes, leading to higher remedy outcomes with fewer unwanted effects. The data of a person’s illness profile may also assist refine affected person choice for scientific trials. Solely these more likely to profit from a remedy might be included, thereby bettering trial outcomes. This strategy will speed up AD drug growth and streamline the method for gaining FDA approval, making certain that efficient therapies attain sufferers extra shortly.
Third, we’re constantly deepening our understanding of the pathological mechanisms of AD to facilitate identification of promising therapeutic targets and drug results in broaden the vary of potential therapeutic approaches for the illness.
Collectively, these efforts maintain nice promise for bettering the analysis, remedy, and total administration of Alzheimer’s illness, main to raised outcomes for sufferers and their households.
Wanting forward, how do you hope your analysis will affect the way forward for Alzheimer’s illness remedy and broader mind well being initiatives?
I hope my work permits early analysis and results in the event of efficient illness modifying therapies and precision drugs approaches. All of those will vastly improve illness administration as sufferers will have the ability to obtain well timed remedy tailor-made to their particular wants.
Over the long run, a holistic strategy in the direction of AD administration is required. This contains elevated consciousness of mind well being and inspiring people to prioritize cognitive wellness all through their lives.
By educating individuals on the significance of early detection and adopting wholesome existence, we are able to empower them to take proactive steps in sustaining their mind well being, probably lowering the private and societal impression of AD.
The place can readers discover extra data?
- The Hong Kong College of Science and Know-how – Research in The Hong Kong College of Science and Know-how ｜Guangdong-Hong Kong-Macao Better Bay Space｜HKUST
- Nancy Ip’s lab homepage – Ip Lab – Molecular Neuroscience Laboratory (hkust.edu.hk)
- Hong Kong Heart for Neurodegenerative Illnesses – https://www.hkcend.org/
About Nancy Yuk-Yu IP, PhD
Nancy Y. IP is the President of The Hong Kong College of Science and Know-how (HKUST) and the Morningside Professor of Life Science. Taking workplace in October 2022, she is the primary feminine president of a publicly funded college in Hong Kong.
Ip obtained her PhD diploma in Pharmacology from Harvard College, after which she held the place of Senior Workers Scientist at Regeneron Prescription drugs Inc. in New York. Since becoming a member of HKUST in 1993, she has served because the Vice-President for Analysis and Improvement, the Dean of Science, and the Head of Biochemistry.
Ip is world-renowned for her vital contributions to the sector of neuroscience in understanding the advanced mechanisms that underlie correct mind capabilities, in addition to drug discovery for neurodegenerative illnesses. Her excellent analysis has resulted in over 330 scientific papers and 70 patents. A distinguished neuroscientist, Ip is an elected member of the Chinese language Academy of Sciences, the US Nationwide Academy of Sciences, and the American Academy of Arts and Sciences, amongst different academies, and is a recipient of quite a few awards and honors, together with the Nationwide Pure Science Awards, the L’OREAL-UNESCO for Girls in Science Award and the ten Science Stars of China by Nature.
As a distinguished neuroscientist, Ip helps form analysis coverage on a world degree. She is a member of assorted strategic initiatives such because the Management Group of the Davos Alzheimer’s Collaborative. Moreover, she actively serves on native committees, such because the Chief Government’s Council of Advisers, to assist steer the strategic growth of Hong Kong. She can be regularly invited to serve on many distinguished organizations. For instance, she was the primary worldwide member elected to the Council of the Society for Neuroscience, the Senior Editor of the Journal of Neuroscience, and a member of the WEF World Agenda Council on Mind Analysis, World Future Council on the Way forward for Neurotechnologies and Mind Science, Dana Alliance for Mind Initiatives, APEC Coverage Partnership on Science, Know-how and Innovation, and IBRO Asia Pacific Area Committee.