Speakers (Part III)

Guests

Prof. Peter CARAVAN

Massachusetts General Hospital & Harvard Medical School

Molecular Magnetic Resonance Imaging Probes for Fibroproliferative Diseases

Many chronic diseases of the heart, liver, lung, intestine, kidney, etc, as well as many cancers, have a fibroproliferative component, i.e. the organ becomes scarred and as scarring increases it causes organ dysfunction.  Current imaging techniques are only sensitive to very advanced stages of fibrosis and no technique can measure disease activity, i.e. whether the injury is ongoing or is old and stable. We have been developing molecular probes, visualizable by MRI, that target components of the extracellular matrix in order to image fibroproliferative diseases and disease activity.  In this lecture I will discuss the chemical requirements for an effective molecular MR probe and show how we have developed and optimized Mn- and Gd-based probes to quantitatively detect disease and measure treatment response in animal models of liver, lung, and kidney disease.    

 

References

  1. Waghorn PA, Jones CM, Rotile NJ, Koerner SK, Ferreira DS, Chen HH, Probst CK, Tager AM, Caravan P. Molecular magnetic resonance imaging of lung fibrogenesis with an oxyamine based probe.  Angew Chem Int Ed. 2017 Aug 7;56(33):9825-9828.
  2. Akam EA, Abston E, Rotile NJ, Slattery HR, Zhou IY, Lanuti M, Caravan P. Improving the reactivity of hydrazine-bearing MRI probes for in vivo imaging of lung fibrogenesis.  Chem Sci. 2020;11:224-231.
  3. Wahsner J, Gale EM, Rodriguez-Rodriguez A, Caravan P. Chemistry of MRI Contrast Agents: Current Challenges and New Frontiers.  Chem Rev. 2019;119(2):957–1057.
  4. Shuvaev S, Akam E, Caravan P. Molecular MR Contrast Agents. Invest Radiol. 2021;56(1):20-34.

Peter Caravan, PhD, is co-director of the Institute for Innovation in Imaging (i3) at Massachusetts General Hospital (MGH) and  Professor of Radiology at Harvard Medical School. He leads a multidisciplinary and translational molecular imaging lab focused on the invention of novel molecular probes and their broad applications in cardiovascular, pulmonary, renal and hepatic diseases, as well as in cancers.  His research spans novel chemistry technologies to advanced MRI and PET imaging in animal models to applications in patient populations. He holds Investigational New Drug (IND) applications for a fibrin-targeted PET tracer and a collagen-targeted PET tracer that are currently being evaluated in 8 clinical trials. He has invented molecular probes specific to fibrogenesis, acidosis, inflammation and thrombosis, as well as gadolinium-free MR contrast agents.

Dr. Caravan received a PhD in Inorganic Chemistry from the University of British Columbia with Prof. Chris Orvig. Following postdoctoral work at the EPFL with Prof. André Merbach, he spent 9 years at Epix Pharmaceuticals developing tissue-specific and responsive MRI contrast agents, one of which, gadofosveset, was approved by the FDA and the EMA. Since joining the MGH in 2007, he has been continuously funded by the National Institutes of Health.

 

Massachusetts General Hospital and Radiology, Harvard Medical School

Email: PCARAVAN@mgh.harvard.edu

Prof. Edward I. SOLOMON

Stanford University

Activating Metal Sites for Biological Electron Transfer

Metal sites in biology often exhibit unique spectroscopic features that reflect novel geometric and electronic structures imposed by the protein that are key to reactivity. The blue copper active site involved in long range, rapid biological electron transfer is a classic example. This talk presents an overview of both traditional and synchrotron based spectroscopic methods and their coupling to electronic structure calculations to understand the unique features of the blue copper active site, their contributions to function and the role of the protein in determining the geometric and electronic structure of the active site (called the “entatic state”). The relation of this active site to other biological electron transfer sites is further developed. In particular ultrafast XFEL spectroscopy is used to evaluate the methionine-S-Fe bond in cytochrome c, and its entatic control by the protein in determining function (electron transfer vs apoptosis).

 

References

Solomon, Edward I.; Jose, Anex; Spiers Memorial Lecture: Activating Metal Sites for Biological Electron Transfer, Faraday Discussion, 2022, 234, 9-30.

Edward I Solomon is the Monroe E. Spaght Professor of Humanities and Sciences at Stanford and a Professor of Photon Science at SLAC National Accelerator Laboratory. He has been a visiting professor in France, Argentina, Japan, China, India and Brazil. He has received ACS National Awards in Inorganic Chemistry, Distinguished Service in the Advancement of Inorganic Chemistry, the Bader Award in Bioinorganic Chemistry, the Ira Remsen Award and the Kosolapoff Medal, the Centenary Medal from the RSC, the Pittsburgh Spectroscopy Award and a range of other recognitions. He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences and a Fellow of   the ACS and the AAAS. Professor Solomon’s research is in the fields of Physical-Inorganic, Bioinorganic, and Theoretical- Inorganic Chemistry.

Stanford University

Email: solomone@stanford.edu

Dr. Jinqing HUANG

Hong Kong University of Science and Technology

Manipulation and Characterization of Biomolecule-metal Complex Interaction at the Single-molecule Level

Metal complexes, especially Pt complexes, have been employed as chemotherapy drugs for various cancer treatments due to their effective anticancer activity. The efficacy of these compounds is, however, undermined by selectivity (off-target binding), toxic side effects, and acquired/intrinsic drug resistance. Thus, it becomes imperative to design new compounds to improve pharmacological potency. Recently, we have developed a novel single-molecule manipulation and spectroscopic characterization platform to identify and quantify the binding between Pt complexes and DNA at the single-molecule level. The non-covalent interactions, in particular, intercalation, are monitored by single-molecule force spectroscopy. The covalent interactions are identified by surface-enhanced Raman spectroscopy. This multi-dimensional characterization can offer subtle details to understand the binding mechanisms between Pt complexes and DNA, which would provide a profound guidance to develop new anticancer drugs targeting specific DNA. Furthermore, our platform also provides additional light sources to trigger light-sensitive compounds, which might open a new door to precisely control the biological processes with high spatiotemporal precision.

 

References

  1. Li, M., Park, B. M., Dai, X., Xu, Y., Huang, J., Sun, F., Nat. Commun. 2022, 13, 3197.
  2. Dai, X., Fu, W., Chi, H., Mesias, V., Zhu, H., Leung, C. W., Liu, W., and Huang, J., Nat. Commun. 2021, 12, 1292.
  3. Li, X., Pei, Y., Zhang, Y., Liu, Y., Fu, W., Li, J., You, H., Huang, J., J. Phys. Chem. B 2020, 124, 42, 9365–9370.

Dr. Jinqing Huang received her B.S. in chemistry from Sun Yat-sen University in 2010 and her Ph.D. in physical chemistry from The University of Hong Kong in 2014, studying the reaction mechanisms and reactive intermediates of photo-sensitive compounds by ultrafast spectroscopy under the supervision of Prof. David Lee Phillips. She then went to Yale University as a postdoctoral associate in biophysical chemistry to develop novel single-molecule spectroscopy and microscopy techniques under the supervision of Prof. Ziad Ganim. Now she is an assistant professor at Department of Chemistry, The Hong Kong University of Science and Technology. Her research interest focuses on developing novel single-molecule manipulation and characterization methods including optical tweezers-based single-molecule force spectroscopy and optical trapping coupled-surface-enhanced Raman spectroscopy and utilizing them to study the heterogeneous biophysical and biochemical processes at the most fundamental level.

The Hong Kong University of Science and Technology

Email: jqhuang@ust.hk

Dr. Yongxin LI

The University of Hong Kong

Genomics-guided and Synthetic Biology-enabled Discovery of New Antibiotics

The emergence of multi-antibiotic resistant pathogens known as “superbugs” is an increasingly severe threat to global health. Ironically, accompanying the worldwide rise of infectious disease is the lack of truly novel antimicrobial in the past three decades. Thus, new effective antimicrobial therapeutics are urgently needed. As chemical discovery from cultured microbes is dwindling in the conventional antibiotic discovery paradigm, exploring the untapped microbial resources has risen as a major focal point for new drug discovery. Genetic interrogation of uncultivated or rare microbes from complex microbiome offers the previously inaccessible biosynthetic capacity of the microbial majority for discovering novel antibiotics. Recent advances in microbial omics analysis and synthetic biology facilitate us to discover antibiotics from the complex microbiome in a culture-independent manner. Our group aims to combine genome mining and synthetic biology to mine and utilize the microbiome’s genetic source for antibiotics discovery. With large-scale metagenome data of ocean and human microbiota publicly available, we want to apply our approaches to harness the microbiome’s chemical potential to enhance the reservoir of antibiotics.

 

References

  1. Li et al. Nature Communications 2018, 9, 3273
  2. Xue et al. Nature Communications 2022, 13, 1647

Dr. Yong-Xin Li finished his Ph.D. in HKUST on the genomics-guided discovery of natural products from marine bacteria. He joined the Department of Chemistry at the University of Hong Kong in 2019 as an Assistant Professor in Chemical Biology. His group uses bioinformatics, synthetic biology, and chemical biology approaches to convert complex microbiota’s genetic potential into chemical reality to discover novel bioactive molecules.

The University of Hong Kong

Email: yxpli@hku.hk

Dr. Seungkyu LEE

The University of Hong Kong

Structure Determinations of Organic Molecules in MOFs by the Single-crystal X-ray Diffraction Technique

The structure determination of newly synthesized organic molecules by the singe-crystal X-ray diffraction (SXRD) technique is an essential step in developing pharmaceuticals. SXRD analysis can unambiguously determine the structures, including the absolute configurations, at the atomic level. However, the SXRD analysis requires sufficiently large single-crystalline samples exhibiting strong X-ray scattering. The large crystal synthesis is non-trivial and accompanies numerous trials and errors. Often, the crystallization is impossible due to the high flexibility and low symmetry of the molecules. The crystallization issue can be alleviated by using the crystalline sponge method. Organic molecules are diffused into the pores of single-crystalline metal-organic frameworks (MOFs) and aligned throughout the crystal. Now, the molecules are crystalline in the pores, and their structures can be determined by the SXRD. In this lecture, Dr. Lee will introduce the crystalline sponge method, which is one of the biological applications of MOFs, and discuss its potential and limitation to be addressed.  

 

References

  1. Inokuma, Y.; Yoshioka, S.; Ariyoshi, J.; Arai, T.; Hitora, Y.; Takada, K.; Matsunaga, S.; Rissanen, K.; Fujita, M. Nature 2013, 495, 461-466.
  2. Lee, S.; Kapustin, E. A.; Yaghi, O. M. Science 2016, 353, 808-811.

Seungkyu Lee has been an Assitant Professor in the Department of Chemistry at the University of Hong Kong since 2021. He received his BSc. at Sungkyunkwan University (SKKU) in 2011 and ME. at KAIST in 2013. He moved to the United States to pursue his chemistry career and received his Ph.D. in chemistry at UC Berkeley in 2018 under the guidance of Prof. Omar M. Yaghi. He was a Postdoctoral Fellow at Northwestern University (2018–2021) with Professor Chad A. Mirkin.

The University of Hong Kong

Email: skchem@hku.hk

Dr. Chun Kit KWOK

City University of Hong Kong

RNA G-quadruplex Function and Targeting

RNA G-quadruplexes (rG4s) have key roles in almost every biological process, including but not limited to transcription, RNA processing, and translation. In this invited talk, we will highlight RNA G-quadruplexes found in coding and non-coding RNA and showcase their diverse functions in cells, and we will demonstrate our lab’s recent efforts to target them selectively using novel L-RNA aptamer tools. Specific examples will be provided in this talk.

 

References

  1.  Lyu, K., Chen, S. B., Chan, C. Y., Tan, J. H., & Kwok, C. K. Structural analysis and cellular visualization of APP RNA G-quadruplex. Chemical Science. 10, 11095 – 11102 (2019).
  2. Chan, C. Y., & Kwok, C. K. Specific Binding of a D‐RNA G‐Quadruplex Structure with an L‐RNA Aptamer. Angew. Chem. Int. Ed. 59, 5293 –5297​ (2020). 
  3. Umar, M.I. & Kwok, C.K. Specific suppression of D-RNA G-quadruplex–protein interaction with an L-RNA aptamer. Nucleic Acids Res. 48, 10125-10141 (2020).
  4. Lyu, K., Chow, E.Y.C., Mou, X., Chan, T. & Kwok, C.K. RNA G-quadruplexes (rG4s): genomics and biological functions. Nucleic Acids Res.  49, 5426-5450 (2021).
  5.  Ji, D., Lyu, K., Zhao, H. & Kwok, C.K. Circular L-RNA aptamer promotes target recognition and controls gene activity. Nucleic Acids Res.  49, 7280-7291 (2021).
  6. Mou, X., Liew, S. W. & Kwok, C.K. Identification and targeting of G-quadruplex structures in MALAT1 long non-coding RNA. Nucleic Acids Res. 50, 397- 410 (2022). 
  7. Umar, M.I., Chan, CY. & Kwok, C.K. Development of RNA G-quadruplex (rG4)-targeting L-RNA aptamers by rG4-SELEX. Nat Protoc. DOI: https://doi.org/10.1038/s41596-022-00679-6 (2022).

Dr. Kit Kwok obtained his B.Sc. in Chemistry (2009) from the Chinese University of Hong Kong, after completing an exchange program at University of California, Los Angeles in 2007-2008. He completed his PhD in Pennsylvania State University (2014), mentored by Professor Philip C. Bevilacqua and Professor Sarah M. Assmann. In Apr 2014, Dr. Kwok worked as a Croucher Postdoctoral Fellow in University of Cambridge under Professor Sir Shankar Balasubramanian. In Oct 2016, Dr. Kwok’s joined the City University of Hong Kong (CityU) as an Assistant professor and has been promoted to Associate professor in July 2021. In 2019, he was one of the recipients of the CityU President Award and Croucher Innovation Award. In 2020, Dr. Kwok’s joined the State Key Laboratory of Marine Pollution, City University of Hong Kong. In 2021, Dr. Kwok was recognized as elected member of Hong Kong Young Academy of Science (YASHK) and Hong Kong Institute for Advanced Study Rising Star in Chemistry.

 Dr. Kwok’s current research focus is to explore the role of RNA structures and interactions in biology, especially the functions of G-quadruplex structures/interactions and non-coding RNA structures/interactions in the mammalian transcriptome and their relevance to gene regulation, RNA metabolism and diseases. Two new research directions in the Kwok lab are to develop targeting tools for detection, imaging, intervention of these important RNA structures and interactions, as well as to invent innovative nucleic acid-based technologies for sensing chemical pollutants and pathogens.

City University of Hong Kong 

Email:

kck0606@gmail.com

Prof. Feng SHAO

National Institute of Biological Sciences

Pyroptosis in Antibacterial and Antitumor Immunity

Pyroptosis is a proinflammatory form of cell death executed by the gasdermin family of pore-forming proteins. Among the family, gasdermin D (GSDMD) is cleaved by canonical inflammasome-activated caspase-1 and LPS-activated caspase-11/4/5. The cleavage unmasks the pore-forming domain in GSDMD that perforates the plasma membrane. GSDMD plays a key role in all inflammasome-mediate immune defenses against various bacterial infections. We further show that GSDME is cleaved by caspase-3, which switches apoptosis to pyroptosis. Using a novel bioorthogonal chemical biology approach that allowed controlled delivery of an active gasdermin into tumors in mice, we found that pyroptosis of < 15% tumour cells could clear the entire 4T1 mammary tumourgraft, which was absent in immune-deficient mice or upon T-cell depletion. Thus, pyroptosis-induced inflammation stimulates potent and effective antitumour immunity. In immune-mediated tumor clearance, cytotoxic lymphocyte relies on granzymes to kill target tumor cells. We found that natural killer cells and cytotoxic T lymphocytes kill GSDMB-positive cells through inducing pyroptosis, mediated by granzyme A (GZMA) cleavage of GSDMB. IFN-g upregulates GSDMB expression and promotes the pyroptotic killing of cancer cells including that by CAR-T and TCR-T cells. Thus, gasdermin-executed pyroptosis serves as a cytotoxic lymphocyte killing mechanism, playing an important role in cancer immunotherapy.

 

References

  1. Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F & Shao F. (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death, Nature (Article), 526, 660–665
  2. Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, Sun H, Wang DC & Shao F. (2016)
    Pore-forming activity and structural autoinhibition of the Gasdermin family, Nature (Article), 535 (7610), 111-116
  3. Wang Y, Gao W, Shi X, Ding J, Liu W, He H, Wang K & Shao F. (2017) Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a Gasdermin, Nature, 547 (7661), 99-103
  4. Wang Q, Wang Y, Ding J, Wang C, Zhou X, Gao W, Huang H, Shao F# & Liu Z# (2020) A bioorthogonal system reveals antitumour immune function of pyroptosis, Nature, 579, 421-426.
  5. Zhou Z, He H, Wang K, Shi X, Wang Y, Su Y, Wang Y, Li D, Liu W, Zhang Y, Shen L, Han W, Shen L, Ding J, Shao F (2020). Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science, 368(6494):eaaz7548.
  6. Broz P, Pelegrín P and Shao F. (2020) The gasdermins, a protein family executing cell death and inflammation. Nature Reviews Immunology, 20,143-157.

Dr. Feng Shao is an investigator and deputy director at National Institute of Biological Sciences (NIBS), Beijing. He was a chemistry undergraduate of Peking University and obtained his PhD from University of Michigan (2003). Before joining NIBS (2005), he was a Damon Runyon Postdoc Fellow at Harvard Medical School. Dr. Shao’s research lies at the interface between bacterial pathogen and host inflammation. He identified most of the known cytosolic receptors for bacterial molecules, including caspase-11/4/5 for LPS and ALPK1 for ADP-heptose in LPS biosynthesis. He also identified gasdermin-D (GSDMD) whose cleavage by caspase-1/4/5/11 determines pyroptosis, critical for septic shock and other inflammatory diseases. His research establishes the gasdermin family of pore-forming proteins, re-defining pyroptosis as gasdermin-mediated programmed necrosis. Among the family, GSDME is activated by caspase-3, which occurs mostly in noncancer cells and contributes to toxicity of chemotherapy drugs. His most recent work demonstrates that pyroptosis is a critical mechanism underlying lymphocyte cytotoxicity and gasdermin activation can stimulate potent antitumor immunity.

Dr. Shao’s work has been recognized by numerous awards including the Future Science Prize, HHMI International Early Career Award and the Protein Society Irving Sigal Young Investigator Award. He is a member of the Chinese Academy of Sciences and the German National Academy of Sciences Leopoldina, an associate member of EMBO, and a fellow of American Academy of Microbiology.

National Institute of Biological Sciences, Beijing

Email: shaofeng@nibs.ac.cn

Prof. Dr. Walter BERGER

Medical University of Vienna

Cancer Metabolism as a Target and Resistance Factor of an Anticancer Ruthenium Compound

“Reprogramming of cellular metabolism” is nowadays considered a hallmark of cancer and a central factor of cancer complexity. It links energetic and epigenetic adaptation with evasion of growth suppression and cell death resistance. However, metabolic alterations in response to and resistance against metal-based anti-cancer therapy are widely enigmatic. To tackle this issue, we combined a multitude of cell/molecular biological analyses with analytical chemistry and multi-omics approaches to dissect the metabolic implications of metal-based chemotherapy. Thereby we focused, in addition to the classical platinum compounds, on the anticancer ruthenium complex sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (BOLD-100). BOLD-100 is an ER-stress inducer currently in multicenter clinical phase II assessment in combination with FOLFOX against gastrointestinal cancers. Moreover, we studied metabolic mechanisms underlying acquired metal-based chemotherapy resistance with the aim to detect combination therapy targets for resistance circumvention. Here we identified major phenotypic differences in acquired resistance to ruthenium compared to platinum drugs. Exemplarily, the metabolic fluxes of fatty acid metabolism, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation were more abundant in BOLD-100- (HCTR) compared to oxaliplatin-resistant (HCT/OxR) HCT116 colon cancer sublines1. Metabolomics and Seahorse analyses identified BOLD-100 as an anti-Warburg drug depleting parental HCT116 cells of lactate and pyruvate. Furthermore, we detected interference of BOLD-100 with cellular lipid metabolism via regulation of lipid droplets (LD) formation. Computational network analysis of gene expression and metabolomics data revealed a clear upregulation of glycolysis in HCTR cells, associated with autophagy deregulation and creating a vulnerability towards glucose deprivation by 2-deoxyglucose (2-DG)2. Moreover, HCTR cells presented a massively increased LD load based on upregulated de novo fatty acid synthesis culminating in a hypersensitivity towards lipid metabolism inhibitors. Exemplarily, the ß-oxidation inhibitor etomoxir efficiently reduced HCTR cell/tumor growth in vitro and in vivo. Furthermore, 2-DG treatment reduced LD levels in HCTR cells, indicating dependence of lipid enrichment on glycolytic activity. Coenzyme A (CoA) is the key metabolite connecting the TCA cycle with lipid metabolism and, consequently, histone acetylation. Importantly, BOLD-100 treatment reduced histone acetylation only in parental HCT116 cells while it enhanced this parameter in HCTR cells. Consequently, mass spectrometric and nuclear magnetic resonance analysis revealed formation of a BOLD-100-CoA thioester under cell-free conditions, which provides a rational explanation for the reduced epigenetic acetylation mark. Combination of BOLD-100 with the CoA-binding compound 4-phenylbutyric acid showed synergistic anticancer activity in several tested cancer models and reversed BOLD-100 resistance. Overall, we have identified a strong metabolic activity of BOLD-100 targeting several central hubs in the complex cellular metabolism network. This bears potential for broad therapeutic applicability of BOLD-100 but warrants further in-depth investigation about the interaction with the onco-metabolism in specific cancer types.

 

References

  1. Galvez L, et al. 2019 Oct 16;11(10):1716-1728. doi: 10.1039/c9mt00141g.
  2. Baier D, et al. 2022 Jan 20;14(2):238. doi: 10.3390/pharmaceutics14020238

Since 11/2013 – Full Professorship for Applied & Experimental Oncology, Medical University Vienna

Since 2010 – Deputy head of the Institute of Cancer Research Vienna

Since 6/2004 – Head of the Research Unit “Development of Experimental Cancer Therapeutics” at the Department of Medicine I, Medical University Vienna

6/2001 – Associate Professor at the Institute of Cancer Research, Medical University Vienna

6/2001 – Habilitation in “Applied and Experimental Oncology” at the Medical Faculty, Vienna University

1998/1999 – Post Doc stay at the Institute of Oncology, Cambridge University, UK (Head: Bruce Ponder)

1993 – 2001 – Post Doc and Assistant professor at the Institute of Tumor Biology/Cancer Research, Dept. Applied and Experimental Oncology, Vienna University

16.12.1993                  Promotion, Dr. rer. Nat/PhD

1989 – 1993 – Product and project management with Hoechst/Austria Company. Education in project and personnel management.

Medical University Vienna

Email: walter.berger@meduniwien.ac.at

Dr. Catherine
Hong Huan HOR

Hong Kong Baptist University

Neurodevelopmental and Pathophysiological Functions of the Primary Cilium

The primary cilium is a non-motile cilium found on the surface of nearly all cell types in vertebrates. It functions primarily as an “antenna’’ on the cell membrane to capture and transduce physical and chemo-signals from extracellular compartments to the cytoplasm and nucleus. Impairment of the primary cilium in vertebrates adversely affects the physiological functions of multiple organs including the brain. In children, defective primary c­­­ilium lead to a class of heritable disorders collectively known as ciliopathies.

 

We decipher the molecular machineries underlying the biogenesis and signal transduction in the primary cilium, particularly, in the context of neurochemistry and neurobiology. We use transgenic mouse mutants and induced-pluripotent stem cells (iPSC) reprogrammed from patient biopsy to establish the disease models of congenital diseases such as ciliopathies. Using these animal and cellular disease models as our research platforms, we uncover a novel causative gene of ciliopathy. Our findings also shed new insights on the neuropathophysiological roles of primary cilium.

 

 

References

  1. Yang Q. J., Wang Z.h., Hor C. H. H., Xiao H. T., Bian Z. X., & Wang J. (2022). Asymmetric synthesis of flavanols via Cu-catalyzed kinetic resolution of chromenes and their anti-inflammatory activity. Science Advances, 8, (22), eabm9603.
  2. Hor, C. H. H.*, Lo, J. C. W., Cham, A. L. S., Leong, W. Y., & Goh, E. L. K.* (2021). Multifaceted Functions of Rab23 on Primary Cilium-Mediated and Hedgehog Signaling-Mediated Cerebellar Granule Cell Proliferation. Journal of Neuroscience, 41(32), 6850-6863.
  1. Zhu, Y., Huang, A., Panczuk, T.,Hor, C. H. H., Wong, K. L., & Li, L. (2021). Persistent luminescence induced by the introduction of multi-valent Mn ions in K2LiBF6 (B= Al, Ga and In) fluoride phosphors. Chemical Engineering Journal,
  1. Lo, J. C. W., Wong, W. L., & Hor, C. H. H. (2021). Efficient and Cost Effective Electroporation Method to Study Primary Cilium-dependent Signaling Pathways in the Granule Cell Precursor. Journal of visualized experiments: JoVE, (177).
  2. Hor, C. H., & Goh, E. L. (2019). Small GTPases in hedgehog signalling: emerging insights into the disease mechanisms of Rab23-mediated and Arl13b-mediated ciliopathies. Current opinion in genetics & development, 56, 61-68.
  3. Tan, C. W., Hor, C. H. H., Kwek, S. S., Tee, H. K., Sam, I. C., Goh, E. L. K., … & Wang, L. F. (2019). Cell surface α2, 3-linked sialic acid facilitates Zika virus internalization. Emerging microbes & infections, 8(1), 426-437

 

Dr. HOR Hong-Huan Catherine (許鳳環) received her Ph.D. from the University of Hong Kong (HKU), studying mouse neural tube patterning and Hedgehog signalling pathway under the supervision of Prof. Mai Har SHAM and Prof. Chi Chung HUI at the Department of Biochemistry. She then embarked on postdoctoral training at the Duke-NUS Medical School Singapore, pursuing research in the realm of developmental and regenerative neuroscience. During which, she was awarded her first individual national funding for young investigator, Young Individual Research Grant from the Ministry of Health, Singapore.

In 2019, Dr. Hor joined Hong Kong Baptist University (HKBU) at the Department of Chemistry as a faculty member. In 2021, she was awarded Collaborative Research Fund (CRF), in which she leads a team of international scientists from Hong Kong, Singapore, and mainland China to investigate the cellular and neurobiology of viral infection. Her research strives to understand the molecular and cellular pathology of hereditary neurological and neuropsychiatric disorders, with particular interest in deciphering the neurochemistry and neurological roles of an instrumental cell-cell signalling organelle, the primary cilium. Her current projects involve mouse disease models, and human iPSCs disease modelling of ciliopathy-like disorders.

 

 

Research interests / Technical expertise:

  • Primary Cilium in Neurodevelopment
  • Neuropathology of Viral Infection
  • Human iPSC & Disease Modelling of Ciliopathy and Neurological Disorders

Hong Kong Baptist University

Email: catherinehor@hkbu.edu.hk