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 modern approaches to Alzheimer’s illness remedy.
Professor Ip highlights immune modulation, mind signaling pathways, and the potential of conventional Chinese language medication in combating neurodegeneration. She additionally displays on how new applied sciences and precision medication are shaping the way forward for Alzheimer’s analysis and the significance of lifelong mind well being.
To begin, might you introduce your self and share what drew you to neuroscience? How did your early analysis on neurotrophic components form your method to learning mind improvement 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 faculty. After incomes my bachelor’s diploma from Simmons Faculty in Boston, I entered graduate faculty at Harvard Medical Faculty, 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 wanting to discover how neurons talk.
My thesis work recognized a novel communication mechanism involving peptides equivalent to VIP and secretin, a big discovering as the one identified neurotransmitters within the mammalian system had been small molecules like acetylcholine. I discovered that these peptides had 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 12 months 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 prospect arose to affix Regeneron, a promising younger startup centered 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 improvement 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 tutorial profession.
My preliminary tutorial analysis aimed to grasp 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 workforce made vital strides in these areas, paving the best way to review Alzheimer’s illness (AD), a situation marked by reminiscence loss. Since synapse loss is a key function of AD, I grew to become considering 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.
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Your analysis on the immune system’s position in Alzheimer’s illness has been groundbreaking. How do you assume these insights might rework the best way we method treating this situation?
Uncovering the position of the immune system in AD pathology has considerably enhanced our understanding of AD pathogenesis. Genetic proof displaying 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 capable of establish new molecular targets and develop novel disease-modifying remedy approaches. This information may also 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 info can be utilized to stratify sufferers with impaired immune capabilities. Thus, focusing on the impaired immune system in AD could possibly be used as a precision medication method.
How would possibly 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 direction of poisonous Aβ to engulf and clear them.
Our research of the IL33/ST2 pathway additionally led to the invention of a novel remedy method. On this research, human knowledge 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 ageing and the immune system is a key focus of your work. How do you assume higher understanding this connection might enhance high quality of life as individuals age?
A greater understanding of this connection, notably how the immune system modifications with growing age, will present necessary insights on methods to handle age-related illnesses in addition to promote wholesome ageing.
Growing old is the strongest danger issue of AD. As Alzheimer’s researchers, it will be important for us to grasp the modifications 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 establish promising targets for drug improvement.
Information of how the immune system modifications with age may also assist in growing preventive measures. This consists of life-style decisions to advertise wholesome ageing, in addition to vaccines and dietary supplements that may improve immune perform and scale back the chance of infections and illnesses.
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You’ve been exploring how synaptic connections may be strengthened to fight neurodegenerative illnesses. What broader impression might these findings have on future remedies for memory-related issues?
Regulation of synaptic power and communication is the essential mechanism underlying reminiscence formation and storage.
Thus, by understanding the mechanisms underlying synapse formation and synaptic plasticity, we will delineate how deregulation of the method contributes to the pathogenesis of memory-related issues. With improved understanding, we will then develop efficient remedies for corresponding memory-related issues.
In your work on drug discovery, together with exploring compounds from conventional Chinese language medication, what potential do you see for these therapies to handle world healthcare challenges in neurodegeneration?
Our drug discovery work has recognized a number of novel molecular targets and plenty of potential drug candidates with varied mechanisms of motion. Our exploration of conventional Chinese language medication (TCM) has additionally recognized compounds or herbs with useful results in AD.
TCM affords a wealth of promising drug candidates supported by its lengthy historical past of use and intensive medical knowledge. We’ve sought to raised perceive the organic actions of the TCM herbs and their lively compounds by evaluating their mechanisms of motion in scientific mannequin techniques.
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 improvement by, pharmaceutical firms. My lab has additionally pioneered a gene remedy expertise for familial AD, which has been licensed for additional improvement.
It needs to be famous that drug improvement is a protracted and arduous course of, and it might be a few years earlier than remedies may be out there for medical use.
Drug improvement for AD is especially difficult as a result of AD is a posh, multifactorial situation involving completely different neuropathological mechanisms and a number of physique techniques. Creating efficient therapies requires an intensive understanding of illness mechanisms.
Luckily, 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 situations, which have expanded illness targets for drug improvement.
In the meantime, new applied sciences equivalent to machine studying and synthetic intelligence are streamlining and accelerating the drug improvement course of. It’s only a matter of time earlier than we have now extra disease-modifying remedies for AD and different neurodegenerative situations.
As Alzheimer’s analysis progresses, how might new remedies focusing on the immune system and mind well being shift the best way we stop or handle the illness in the long run?
Historically, a lot of Alzheimer’s drug improvement efforts have centered 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 improvement, equivalent to restoring impaired immune perform in AD and addressing neuroinflammation.
This shift in focus will result in the event of latest lessons of illness modifying remedies. As an illustration, therapies would possibly goal particular immune cells or pathways that contribute to neurodegeneration to mitigate the inflammatory processes that exacerbate cognitive decline.
Immune-targeted methods is also used alongside current medication to offer complete remedy choices that each alleviate signs and modify illness trajectory.
With speedy 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 issues at a speedy tempo, and accelerating progress within the improvement of latest remedies and therapies. As an illustration, advances in neuroimaging are offering unprecedented insights into mind exercise and connectivity.
New applied sciences are additionally serving to to disclose the organic modifications in mind cells at a single-cell degree and inside a spatial context. This development helps us delineate the pathological mechanisms of AD in larger element.
Different advances embrace modern genetic and molecular instruments equivalent to CRISPR and different gene-editing applied sciences to govern genes linked to neurological issues, which might result in focused therapies for situations equivalent to familial AD.
In the meantime, machine studying and synthetic intelligence are serving to researchers analyze huge quantities of neuroimaging and genetic knowledge, establish patterns, and develop predictive fashions to additional support and speed up analysis efforts.
As you’re employed on the frontlines of neuroscience innovation, what upcoming developments within the area do you imagine can have the best impression on society?
We’re enthusiastic about plenty of upcoming developments. The primary is early prognosis of AD – figuring out sufferers when the illness remains to be in its early stage and treatable.
Presently, AD is primarily recognized by cognitive assessments however by the point cognitive decline is obvious, the illness has progressed to a complicated stage. Early prognosis is a game-changer, permitting for well timed medical interventions that may result in higher remedy outcomes, thus enhancing the standard of life for sufferers.
The second is the power to stratify AD sufferers into illness subtypes for improvement of precision medication approaches. This may assist establish appropriate candidates for focused drug remedy in medical trials with particular disease-modifying medication.
With precision medication, sufferers will obtain tailor-made remedies primarily based on their particular person genetic profiles and illness subtypes, leading to higher remedy outcomes with fewer uncomfortable side effects. The data of a person’s illness profile may even assist refine affected person choice for medical trials. Solely these more likely to profit from a remedy will probably be included, thereby enhancing trial outcomes. This method will speed up AD drug improvement and streamline the method for gaining FDA approval, making certain that efficient remedies attain sufferers extra shortly.
Third, we’re repeatedly deepening our understanding of the pathological mechanisms of AD to facilitate identification of promising therapeutic targets and drug results in develop the vary of potential therapeutic approaches for the illness.
Collectively, these efforts maintain nice promise for enhancing the prognosis, remedy, and general 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 allows early prognosis and results in the event of efficient illness modifying remedies and precision medication approaches. All of those will tremendously 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 method in direction of AD administration is required. This consists of 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 will empower them to take proactive steps in sustaining their mind well being, doubtlessly lowering the private and societal impression of AD.
The place can readers discover extra info?
- The Hong Kong College of Science and Know-how – Examine 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 Middle 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 acquired her PhD diploma in Pharmacology from Harvard College, after which she held the place of Senior Employees Scientist at Regeneron Prescribed drugs Inc. in New York. Since becoming a member of HKUST in 1993, she has served because the Vice-President for Analysis and Growth, 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 complicated 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 Ladies 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 improvement of Hong Kong. She can also be often invited to serve on many outstanding 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.
