HMS-CSSA Lightning Talks

Guoping Wang, Ph.D.

Current Position:

Postdoctoral Fellow

Broad Institute of MIT and Harvard

Biography:

Dr. Guoping Wang earned his Bachelor's degree in Life Sciences from Nankai University in 2016. He went on to earn his Ph.D. in Medical Sciences from the Chinese University of Hong Kong (CUHK) in 2022. His Ph.D. research revolved around the development of a novel droplet microfluidics platform for single virus and bacteria genome sequencing. Currently, Dr. Wang is a postdoctoral associate at the Broad Institute of MIT and Harvard, working on developing new techniques and methodologies to enhance our understanding of complex biological systems. This involves the application of long-read sequencing, large-scale single-cell techniques, and synthetic biology. Dr. Wang commits to fostering diverse collaborations to address significant scientific challenges and advance discoveries in biomedical sciences.

Talk title: 

Diving into Single-cell Sequencing

Abstract: 

Single-cell sequencing has revolutionized our understanding of cellular heterogeneity by providing a micro-level perspective over the past decades. Although heterogeneity is essential for various biological communities, the currently demonstrated platform predominantly focuses on eukaryotic cells without cell walls and their transcriptomics, leaving significant gaps in the study of omics from other single biological entities such as bacteria and viruses. Due to the difficulty of isolating and acquiring their DNA, contemporary methodologies for the characterization of generic biological entities remain conspicuously constrained, with low throughput, compromised lysis efficiency, and highly fragmented genomes6. Herein, we present the Generic Single Entity Sequencing platform (GSE-Seq), which boasts ample versatility, high throughput, and high coverage, and is enabled by an innovative workflow, addressing the critical challenges in single entities sequencing: (1) one-step manufacturing of massive barcodes, (2) degradable hydrogel-based in situ sample processing and whole genome amplification, (3) integrated in-drop library preparation, (4) compatible long-read sequencing. By GSE-Seq, we have achieved a significant milestone by enabling high-throughput, long-read single-entity profiling of dsDNA and ssDNA from single virus sequencing (SV-seq) and single bacteria sequencing (SB-seq) of the human gut and marine sediment for the first time. Notably, our analysis uncovered previously overlooked viral and bacterial dark matter and phage-host interactions. In summary, the presented conceptually new workflow offers a toolbox based on droplet microfluidics to tackle the persistent challenges in high-throughput profiling to generic applications, which hold immense promise for diverse biological entities, especially hard-to-lyse cells.

Highlighted publications:

(Believe it or not, I've yet to debut as the lead author in the academic spotlight.)

1. (Patent) US Application No: 63/424,809 METHODS AND COMPOSITIONS FOR NUCLEIC ACID ANALYSIS

2. (Patent) CN Application No: 202310290106.9 一种用于核酸的分析方法和组合物

3. (BioRxiv and under revision) Guoping Wang, Liuyang Zhao,Yu Shi, Fuyang Qu, Yanqiang Ding,Weixin Liu, Changan Liu, Gang Luo, Meiyi Li, Xiaowu Bai, Luoquan Li, Yi-Ping Ho, Jun Yu. High-throughput generic single-entity sequencing using droplet microfluidics. (2023)

4. Ding, Yanqiang, Liuyang Zhao, Guoping Wang, Yu Shi, Gang Guo, Changan Liu, Zigui Chen, Olabisi Oluwabukola Coker, Junjun She, and Jun Yu. PacBio sequencing of human fecal samples uncovers the DNA methylation landscape of 22 673 gut phages. Nucleic Acids Research (2023)

5. Yufeng Lin, Guoping Wang, Jun Yu, and Joseph JY Sung. "Artificial intelligence and metagenomics in intestinal diseases." Journal of Gastroenterology and Hepatology. (2021)

Bin Song, MD, Ph.D.

Current position: 

Scientific Director, George Lopez Laboratory for Regenerative Cell Therapy,

Department of Neurosurgery, Massachusetts General Hospital

Biography:

Dr. Song is currently a PI at the Department of Neurosurgery, MGH. She received her Bachelor degree in clinical medicine at Wuhan university in 2002, and her Ph.D. degree in Pharmacology at Sun Yat-sen University in 2008. She then joined Sun Yat-Sen University as a Lecturer and subsequently as an Associate Professor. In 2014, she worked as a postdoctoral researcher at McLean Hospital, Harvard Medical School. Later she joined the faculty team as an Instructor in Psychiatry. In 2020, she established her own lab at the Institute for Translational Brain Research, Fudan University. From Oct 2023, she returned back to Harvard ecosystem and accepted the position of Scientific Director of George Lopez Laboratory for Regenerative Cell Therapy. Dr. Song’s research focuses on translational neuroscience and cell replacement therapy for Parkinson’s Disease. 

Talk title:

From Bench to Bedside: Pioneering Stem Cell-Based Therapy for Parkinson’s Disease

Abstract: 

Parkinson’s Disease (PD) affects 1-2% of the population over the age of 65. Loss of midbrain dopamine neurons (DANs) is a key pathological feature. Dopamine-replacement therapy (e.g., L-dopa and/or DA agonists) and deep brain stimulation are the current standard treatments. However, these treatments are symptomatic and cannot halt or slow down the disease progression. Stem cell-based therapy to replace the lost DANs is a promising approach for PD, and patient-autologous hiPSCs represent a superior cell source negating the need for immunosuppression. In 2018, the Department of Neurosurgery, MGH and the Laboratory of Molecular Neurobiology at McLean Hospital, jointly completed the world's first FDA-approved autologous hiPSC-differentiated dopamine precursor cell implantation for the treatment of PD (N Engl J Med. 2020). The patient receiving treatment was Dr. George Lopez. To honor his contribution, in 2023, the Lopez Lab was established at MGH, with its own self-contained GMP facility to produce clinical-grade cells for an upcoming autologous PD cell therapy clinical trial, and a neurobiology laboratory to implement next generation cell therapy strategies. This talk will introduce the history, present and future of PD cell therapy.

Highlighted publications:

(* denotes equal contribution)

1. Xue J, Wu YF, Bao YT, Zhao ML, Li FZ, Sun J, Sun YM, Wang J, Chen L, Mao Y, Schweitzer JS, Song B. Clinical Considerations in Parkinson’s Disease Cell Therapy. Ageing Res. Rev. 2023; 83:101792.

2. Song B, Feldmann J, Cao S, Feitosa F, Kong Y, Kim W, Schweitzer A, Leblanc P, Schweitzer JS and Kim KS. A Pitx3-deficient developmental mouse model for fine motor, olfactory, and gastrointestinal symptoms of Parkinson’s disease. Neurobiol. Dis. 2022; 170:105777.

3. Song B, Cha Y, Ko S, Jeon J, Lee N, Seo H, Park KJ, Lee IH, Lopes C, Feitosa M, Luna MJ, Jung JH, Kim J, Hwang D, Cohen BM, Teicher MH, Leblanc P, Carter BS, Kordower JH, Bolshakov VY, Kong SW, Schweitzer JS, Kim KS. Human autologous iPSC-derived dopaminergic progenitors restore motor function in Parkinson’s disease models. J. Clin. Invest. 2020;130:904-920. 

4. Schweitzer JS*, Song B*, Herrington TM*, Park T-Y*, Lee N, Ko S, Jeon J, Cha Y, Kim K, Li Q, Henchcliffe C, Kaplitt M, Neff C, Rapalino O, Seo H, Lee I-H, Kim J, Kim T, Petsko GA, Ritz J, Cohen BM, Kong SW, Leblanc P, Carter BS, Kim KS. Personalized iPSC-derived Dopamine Progenitor Cells for Parkinson’s Disease. N. Eng. J.Med. 2020; 382:1926-1932. 

Full publication list can be found here:

https://www.ncbi.nlm.nih.gov/myncbi/song.bin.1/bibliography/public/

Ying Dong, Ph.D.

Current position: 

Research fellow

Program in Cellular and Molecular Medicine at Boston Children's Hospital

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School

Biography:

Dr. Dong received her Ph.D. degree with Dr. James J. Chou from the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, and studied the structure and function of membrane proteins. As a postdoctoral fellow with Dr. Hao Wu at Boston Children’s Hospital, she broadened her research focus to explore immunity. Dr. Dong is particularly interested in understanding the molecular interactions governing immune signaling responses, particularly those mediated by immune receptors and signaling complexes, with a focus on deciphering their structural basis, function, and regulation. Her research aims to provide potential implications for understanding diseases and developing therapeutics. Her study is awarded by Charles A. King Trust fellowship.

Talk title:

Structural transitions enable IL-18 maturation and signaling

Abstract: 

Interleukin-1 (IL-1) family cytokines are key regulators of inflammation and host defense. Unlike most cytokines, several IL-1 family members, including IL-1β and IL-18 are synthesized as non-inflammatory pro-proteins. Only upon cleavage, typically by inflammasome-associated caspases, is the inflammatory activity of IL-1β and IL-18 unveiled. A structural explanation of how pro-IL-1 family cytokines are selected as substrates for caspase cleavage, and why cytokine cleavage is necessary for inflammatory activity, is unclear. Here, we report the cryogenic electron microscopy (cryo-EM) structure of caspase-1 in complex with pro-IL-18, and the nuclear magnetic resonance (NMR) structure of apo pro-IL-18. Our studies reveal the molecular mechanisms for the complete pathway of recognition and cleavage of pro-IL-18 by human caspase-1 and suggest diverse ways with which inflammatory caspases process their substrates.

Highlighted publications: 

(*denotes co-first authors)

1. Dong Y*, Bonin JP*, Devant P*, Liang Z, Sever AI, Mintseris J, Aramini JM, Gang D, Gygi SP, Kagan JC, Kay LE, Wu H. Structural transitions enable IL-18 maturation and signaling. Immunity (2024, accepted). 

2. Devant P*, Dong Y*, Mintseris J, Ma W, Gygi SP, Wu H, Kagan JC. Structural insights into cytokine cleavage by inflammatory caspase-4. Nature (2023).

3. Dong Y*, Pi X*, Bartels-Burgahn F, D Saltukoglu, Liang Z, Yang J, Alt F. W, Reth M, Wu H, Structural principles of B-cell antigen receptor assembly. Nature (2022). 

4. Fontana P*, Dong Y*, Pi X*, Tong AB*, Hecksel CW, Wang L, Fu TM, Bustamante C, Wu H.  Structure of the cytoplasmic ring of the nuclear pore complex by integrative cryo-EM and AlphaFold prediction. Science (2022).

5. Oxenoid K*, Dong Y*, Cao C*, Cui T*, Sancak Y, Markhard AL, Grabarek Z, Kong L, Liu Z, Ouyang B, Cong Y, Mootha VK, Chou JJ. Architecture of the mitochondrial calcium uniporter. Nature (2016). 

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