Hao Chi

Director of Innovative Drug （pharmacology）

Being involved in multiple projects development in the early phase, then shifted to mainly working on NLRP3 inflammasome inhibitors evaluations since April 2023 (Ref: patent WO2025113692A1), along with several other projects involving small peptide and small molecule drugs development. Currently the team that I am responsible to consists of six people including me, two pharmacologists, two animal technicians, and one cell biology technician. We are responsible for the whole biological evaluations of the project, including compounds screening, in vitro/in vivo drug efficacy evaluations, pharmacokinetics evaluations, even concerning some toxicology evaluations. For the project, we started from the ground. Based on our initial literature studies and discussions with the supervisors, we confirmed the potential druggable target (NLRP3 inflammasome) and built the corresponding cellular models to validate the target and performing the compounds screenings. Since then, we built different diseases animal models to explore the potential indications and the PK studies to further screening our leads. After that, we gradually shift our models to suit with two different indications and eventually into one indication, at that point the PCC is determined. Then a systematic drug efficacy evaluation was initiated and the corresponding toxicology and pharmacokinetics evaluations for IND enabling were also initiated. Currently, the systemic in vivo drug efficacy evaluations have been established and the majority of the work has been down, and the corresponding documents for IND enabling are being prepared. During the exploration of indications and the systemic drug efficacy evaluations, I have been working on immunology, metabolisms, and neuronal related researches methods studies and molecular mechanisms studies.

*Responsible for all the AD related projects of the lab, including investigating the process of autophagic degradation of TDP-43. We found several potential LC3 interaction regions (LIR) motifs. We first validated the effects of the LIR sites on modulating TDP-43 autophagic degradation and toxicity in vitro and then test it in vivo using Drosophila as the model. The other projects including investigating the role of GPR50 in regulating BACE1 autophagic degradation; clemastine treatment on modulating oligodendrocytes in AD mice model; The role of DISC1 on modulating the activity of microglia, etc. *Writing grants application, training the students.

• First project: Focused on T cells based chimeric antigen receptor (CAR) design, virus packaging and cell transduction, ex vivo cell expansion and CAR detection using FACS. • Second project: Focused on adopting oncolytic adenovirus for ovarian cancer treatment, aiming to sensitize the tumor for chemotherapy through virus disseminating shRNA for ALDH1A1, using cell lines SKOV3, OVCAR3 as the model.

Responsibilities: • Responsible for developing molecular diagnostic kits, including p53, p63 protein detection kits and gene mutation detection kits (EGFR, KRAS, BRAF) • Compose production quality testing documents and registration documents Achievements: • Applied immunological histological chemistry technology to develop antigen detection combination kit for assisting lung cancer diagnosis，completed systematic optimization of the experiment process; • Applied quantitative PCR technology to develop technology to develop gene mutation detection kits to assist personalized medicine, finished the project proposal and defined the technical proposal and started the systematic optimization of the experiment process

• Investigating the impact of different posttranslational modifications including phosphorylations and truncation on modulating tau protein toxicity using drosophila as the model. We generated transgenic flies to overexpress human tau proteins using different neuronal drivers and using microscopies to observe the pathologies it induced, and study the behavior changes as well as protein levels changes. We found that both hyperphosphorylation and hypophosphorylation can increase tau toxicity and the tau truncation at Asp421 under hyperphosphorylation condition reduced tau protein toxicity, which is related to a change of tau protein distribution within the neuron.

09/2014-06/2015 Master degree project: in an experimental epilepsy group (epilepsy center, department of clinical sciences, Lund University Hospital) • Participated in the research projects of in vitro direct conversion of fibroblasts into neurons (both mouse and human fibroblasts), focusing on their properties in the in vitro epileptic model (Organotypic cultures). I am responsible for the conversion of the mouse fibroblasts, hippocampal dissection and the slicing, culturing of the slices and also electrophysiology recordings, following immunostainnings. • Participated in the research project of in vitro testing the properties of novel inhibitory channelrodopsins, applied in treating epilepsy. I am responsible for electrophysiology recording of the slices (both field recording and single cell patch clamp) and the following immunostainning

12/2011/-05/2012 Bachelor degree project • Conducted the research on the effect of acidifier on the weaned young rabbits' health 03/2011-03/2012 Undergraduate innovation research project • Participated in the research project held by the graduate students on cultivating porcine male germ-line stem cells in vitro to improve the culture environment and study the involved signal transduction