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 elements, and modern approaches to Alzheimer’s illness therapy.
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 elements form your strategy to finding out 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 faculty. After incomes my bachelor’s diploma from Simmons Faculty in Boston, I entered graduate faculty 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 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 possibility arose to hitch Regeneron, a promising younger startup centered on neurodegenerative illnesses, I took it. At Regeneron, I labored on neurotrophic elements 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 elements, showcasing their function in neural growth and plasticity. Regeneron’s contributions have had a long-lasting affect 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 elements 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 crew made important 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 turned fascinated with investigating how dysregulation of neurotrophic elements contributes to synapse loss and impaired synaptic operate 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 function in Alzheimer’s illness has been groundbreaking. How do you suppose these insights may remodel the way in which we strategy treating this situation?
Uncovering the function 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 in a position to establish new molecular targets and develop novel disease-modifying therapy approaches. This information can even 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 features. 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 operate 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 therapy 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 sort within the mind, in direction of poisonous Aβ to engulf and clear them.
Our examine of the IL33/ST2 pathway additionally led to the invention of a novel therapy 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 features 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 getting older and the immune system is a key focus of your work. How do you suppose higher understanding this connection may 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 vital insights on the right way to handle age-related illnesses in addition to promote wholesome getting older.
Getting old is the strongest threat issue of AD. As Alzheimer’s researchers, it is necessary for us to grasp the modifications in particular immune biomarkers as people age and decide whether or not any of them function pathological elements or contribute to the pathogenesis of AD. Clearer understanding of how these biomarkers contribute to illness will assist establish promising targets for drug growth.
Data of how the immune system modifications with age can even assist in creating preventive measures. This consists of way of life selections to advertise wholesome getting older, in addition to vaccines and dietary supplements that may improve immune operate and cut back the danger of infections and illnesses.
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You’ve been exploring how synaptic connections might be strengthened to fight neurodegenerative illnesses. What broader affect may these findings have on future therapies for memory-related issues?
Regulation of synaptic power and communication is the fundamental 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 therapies for corresponding memory-related issues.
In your work on drug discovery, together with exploring compounds from conventional Chinese language drugs, what potential do you see for these therapies to deal with world healthcare challenges in neurodegeneration?
Our drug discovery work has recognized a number of novel molecular targets and a variety of potential drug candidates with varied mechanisms of motion. Our exploration of conventional Chinese language drugs (TCM) has additionally recognized compounds or herbs with helpful results in AD.
TCM affords a wealth of promising drug candidates supported by its lengthy historical past of use and intensive medical 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 techniques.
A few of the potential drug leads my lab has recognized/developed present important promise in treating AD. These are both in co-development with, or have been licensed for additional growth by, pharmaceutical corporations. My lab has additionally pioneered a gene remedy know-how for familial AD, which has been licensed for additional growth.
It needs to be famous that drug growth is an extended and arduous course of, and it might be a few years earlier than therapies might be obtainable for medical use.
Drug growth for AD is especially difficult as a result of AD is a posh, multifactorial situation involving totally different neuropathological mechanisms and a number of physique techniques. Growing efficient therapies requires an intensive understanding of illness mechanisms.
Thankfully, lately, our understanding of AD and different neurodegenerative illnesses has grown significantly. International large-scale analysis collaborations are unraveling the complexities of those situations, which have expanded illness targets for drug growth.
In the meantime, new applied sciences equivalent to machine studying and synthetic intelligence are streamlining and accelerating the drug growth course of. It is just a matter of time earlier than now we have further disease-modifying therapies for AD and different neurodegenerative situations.
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 centered on the 2 hallmark options of the illness: amyloid plaques and tau tangles. New understanding of the function of the immune system in AD is unveiling new molecular targets and new methods for drug growth, equivalent to restoring impaired immune operate in AD and addressing neuroinflammation.
This shift in focus will result in the event of latest 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 is also used alongside present medication to supply complete therapy 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 therapy 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 fast tempo, and accelerating progress within the growth of latest 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 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 control genes linked to neurological issues, which may 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 information, establish 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 subject do you imagine may have the best affect on society?
We’re enthusiastic about a variety of upcoming developments. The primary is early analysis of AD – figuring out sufferers when the illness continues to be in its early stage and treatable.
At the moment, AD is primarily recognized via 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 medical interventions that may result in higher therapy outcomes, thus enhancing 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 establish appropriate candidates for focused drug therapy in medical trials with particular disease-modifying medication.
With precision drugs, sufferers will obtain tailor-made therapies based mostly on their particular person genetic profiles and illness subtypes, leading to higher therapy outcomes with fewer unwanted side effects. The data of a person’s illness profile will even assist refine affected person choice for medical trials. Solely these more likely to profit from a therapy might be included, thereby enhancing trial outcomes. This strategy will speed up AD drug growth and streamline the method for gaining FDA approval, guaranteeing that efficient therapies attain sufferers extra rapidly.
Third, we’re repeatedly 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 enhancing the analysis, therapy, and total administration of Alzheimer’s illness, main to raised outcomes for sufferers and their households.
Trying forward, how do you hope your analysis will affect the way forward for Alzheimer’s illness therapy and broader mind well being initiatives?
I hope my work allows 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 be capable to obtain well timed therapy tailor-made to their particular wants.
Over the long run, a holistic strategy 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, probably decreasing the non-public and societal affect of AD.
The place can readers discover extra data?
- 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 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 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 important contributions to the sector of neuroscience in understanding the advanced mechanisms that underlie correct mind features, 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 worldwide 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 incessantly 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 International Agenda Council on Mind Analysis, International 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.