Genetics seminars

Junjie Guo investigates how an intronic nucleotide-repeat expansion in C9orf72 causes familial and some sporadic cases of amyotrophic lateral sclerosis and frontotemporal dementia. The talk presents progress in understanding how the expansion changes gene expression, alongside functional-genomics approaches that identify potential therapeutic targets controlling expression of the pathogenic mutation. It also considers which mechanisms and modifiers extend to other disease-causing repeat expansions. Guo is Associate Professor of Neuroscience at Yale School of Medicine; the seminar is hosted by J. Wren Kim. Online via CUNY ASRC Zoom. Thursday 8 October 2026, 12:00–13:00 EDT (America/New_York; UTC−4). Follow the Zoom link on the official seminar page; meeting details are also supplied in its abstract PDF. Organized by the Advanced Science Research Center at the CUNY Graduate Center, Neuroscience Initiative. This listing advertises remote attendance.

Mariana Wolfner presents research on the molecular changes in eggs, sperm, and females that coordinate successful reproduction, drawing on genetic and physiological studies of fertilization. This NIH Wednesday Afternoon Lecture Series event is offered in person and through NIH VideoCast.

Shiv Grewal discusses how chromatin and epigenetic mechanisms establish, maintain, and transmit genome states beyond the DNA sequence itself. This NIH Wednesday Afternoon Lecture Series event is offered in person and through NIH VideoCast.

UC Berkeley Molecular & Cell Biology seminar (Division of Genetics, Genomics & Development) by Barak Cohen of Washington University in Saint Louis on massively parallel experimental studies of enhancer function.

Convergence Seminar by Alexis Battle, PhD (Wu and Zhang Professor of Biomedical Engineering and Computer Science, Johns Hopkins University), on computational and machine-learning approaches for analyzing how genetic variation impacts gene regulation and disease, including noncoding sequences and rare variants.

Jiaqi Zhang examines how computational models can learn the effects of genetic interventions from single-cell experiments. Such experiments reveal causal relationships, but their high-dimensional measurements are costly to collect and difficult to interpret. The seminar connects identifiable causal representations with a predictive method for previously unseen perturbations. The approach incorporates prior biological knowledge and changes in data distributions to estimate responses at individual-cell resolution. It also uses predictions to guide subsequent experiments. An application identifies and experimentally validates previously unknown T-cell regulators with potential relevance to cancer immunotherapy. The recording follows the original July seminar; the series lists Zhang at MIT, while the recording biography describes her incoming Columbia appointment.

Shimon Sakaguchi, Mary E. Brunkow and Fred Ramsdell explain how peripheral immune tolerance prevents the immune system from attacking the body. Sakaguchi follows the identification of regulatory T cells, the CD25 marker, and the relationship between central tolerance and active suppression of self-reactive cells. He considers how changing regulatory T-cell activity could support cancer treatment and transplantation. Brunkow describes genetic investigation of scurfy mice, identification of FOXP3, and the connection between mutations in this gene and human IPEX syndrome. The work establishes a molecular basis for the development and function of regulatory T cells. Ramsdell traces the move from these basic discoveries toward therapeutic strategies, including engineering a patient’s regulatory T cells to target inflammation in rheumatoid arthritis. He discusses early clinical investigation and the ambition of restoring immune balance; these approaches are presented as developing treatments rather than established cures.

David Reich examines how sequencing DNA from ancient human remains has changed the reconstruction of population history. Genetic evidence from past cultures can reveal relationships and movements that are difficult to infer from living populations alone, sometimes challenging interpretations based on archaeology, language and written history. The lecture explores what these discoveries imply for understanding shared and complex human ancestries, and how knowledge of the past could inform the study of human health. A discussion with Carl Zimmer connects the research to the interpretation and communication of evidence about human history. The programme extends the paleogenomic research associated with the 2022 medicine prize through recent work on ancient and modern human DNA.

A hallmark pathological feature of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion of RNA-binding protein TDP-43 from the nucleus of neurons in the brain and spinal cord. A major function of TDP-43 is as a repressor of cryptic exon inclusion during RNA splicing. By re-analyzing RNA-sequencing datasets from human FTD/ALS brains, we discovered dozens of novel cryptic splicing events in important neuronal genes. Single nucleotide polymorphisms in UNC13A are among the strongest hits associated with FTD and ALS in human genome-wide association studies, but how those variants increase risk for disease is unknown. We discovered that TDP-43 represses a cryptic exon-splicing event in UNC13A. Loss of TDP-43 from the nucleus in human brain, neuronal cell lines and motor neurons derived from induced pluripotent stem cells resulted in the inclusion of a cryptic exon in UNC13A mRNA and reduced UNC13A protein expression. The top variants associated with FTD or ALS risk in humans are located in the intron harboring the cryptic exon, and we show that they increase UNC13A cryptic exon splicing in the face of TDP-43 dysfunction. Together, our data provide a direct functional link between one of the strongest genetic risk factors for FTD and ALS (UNC13A genetic variants), and loss of TDP-43 function. Recent analyses have revealed even further changes in TDP-43 target genes, including widespread changes in alternative polyadenylation, impacting expression of disease-relevant genes (e.g., ELP1, NEFL, and TMEM106B) and providing evidence that alternative polyadenylation is a new facet of TDP-43 pathology.

Anne Ferguson-Smith examines the layer of epigenetic information that influences how the DNA sequence is used. Research on this layer has changed understanding of genome function, responses to the environment and possible inheritance beyond DNA sequence alone. The lecture considers how epigenetics affects genes and contributes to modern medicine, while asking which widely held claims are supported by evidence and which deserve renewed scrutiny.

Pluripotent cells, including embryonic stem (ES) and induced pluripotent stem (iPS) cells, are used to investigate the genetic and epigenetic underpinnings of human diseases such as Parkinson’s, Alzheimer’s, autism, and cancer. Mechanisms of somatic cell reprogramming to an embryonic pluripotent state are explored, utilizing patient-specific pluripotent cells to model and analyze neurodegenerative diseases.

Victor Ambros and Gary Ruvkun recount how studies of developmental timing in the nematode C. elegans revealed a new mechanism for regulating genes. The lectures follow the genetic analysis of lin-4 and lin-14, the discovery that a regulatory gene could produce a short non-coding RNA, and the connection between that RNA and complementary sequences in a target messenger RNA. They then examine how the discovery of additional microRNAs, including conserved regulators, changed a seemingly specialised worm finding into a widespread principle of gene regulation. The programme explains how small RNAs influence protein production after transcription and how experiments in a model organism exposed a regulatory system important across multicellular life.