In this deep dive, we break down the journey of the PIM Kinase target. We explore the complex PIM1 molecular mechanism, examine why first-generation pan-PIM inhibitors like AZD-1208 faced safety issues and a lack of monotherapy efficacy, and reveal the final clinical verdict of the Terminated and Completed Phase 1 studies.
📖 Video Chapters:
0:00 - Intro
1:05 - Biobanks Associations for PIM1
22:18 - PIM1 Gene
39:00 - PIM1 Protein
52:52 - PIM1 Known Drugs and Clinical Trials
Disclaimer: This video is for educational purposes only and should not be used for medical diagnosis or treatment decisions. Always consult with healthcare professionals for medical advice.
In this episode, we explore the association between the PEAR1 gene and various platelet disorders. Using data and research, we aim to explain the significance of platelet count and the effects of thrombocytopenia and low platelets in these conditions. This includes genetic analysis of the genome.
KGWAS is a novel geometric deep learning method that leverages a massive functional knowledge graph across variants and genes to significantly improve detection power in small-cohort GWASs. Thank you, Kexin Huang and Martin Jinye Zhang, for joining me on this one.Preprint:https://www.medrxiv.org/content/10.11...GitHub Page:https://github.com/snap-stanford/KGWASOfficial Website:https://kgwas.stanford.edu/
📖 Video Chapters:0:00 - Introduction to Rare Disease Genetics Problem0:54 - Welcome & Paper Overview1:22 - What is KGWAS? The Elevator Pitch2:41 - Why Finding More GWAS Hits Matters4:46 - Origin Story: Collaboration with GSK6:09 - Knowledge Graph Architecture Overview7:36 - Building the Variant-Gene-Pathway Network9:55 - Handling Linkage Disequilibrium (LD) Challenges13:55 - Training the Large-Scale Graph Neural Network14:16 - Model Training Requirements and Scalability15:22 - Open Source Availability and Accessibility16:05 - Scaling to Whole Genome Analysis17:12 - Figure 2: Validation Through Simulations18:24 - UK Biobank Downsampling Experiments20:04 - Precision-Recall Performance Results21:00 - Figure 3: Real-World Disease Applications21:38 - Ulcerative Colitis Case Study Example22:48 - Experimental Validation of Ulcerative Colitis Discovery24:03 - Myasthenia Gravis Case Study Analysis26:10 - Knowledge Graph Component Analysis and Ablation Studies27:54 - Tissue-Specific vs Context-Agnostic Approaches32:03 - Figure 4: Network Interpretation and Attention Mechanisms36:30 - Alzheimer's Disease Network Visualization40:01 - Drug Development Applications and Implications41:15 - Post-GWAS Era Applications and End-to-End Solutions43:01 - Figure 5: Compatibility with Existing GWAS Tools48:16 - Population Diversity and Cross-Ancestry Applications49:41 - Future Directions and Technical Improvements52:16 - Input/Output Requirements and Computational Resources54:28 - Website Demo and Interactive Features56:59 - PhD Student Advice and Research Philosophy59:36 - Closing Remarks
This podcast was made possible by CIUT-FM 89.5, University of Toronto Community Radio. For more content visit https://ciut.fm/
Link to the paper:
https://www.nature.com/articles/s41586-025-08916-0
Join me in a conversation with two of the authors, Lakshmi Mahendrawada and Steven Hahn.
This podcast was made possible by CIUT-FM 89.5, University of Toronto Community Radio. For more content, visit https://ciut.fm/
Join us for this comprehensive masterclass episode as we explore the fascinating world of K562 cells with Dr. Tom Karagiannis, who has worked with these remarkable cells for almost three decades. From his first encounter with them as a young researcher in 1996 during the exciting era of targeted therapy development, Dr. Karagiannis shares both the scientific breakthroughs and practical realities of working with these "weeds" of the lab.
📖 Video Chapters:
0:00 - The 1917 Origin Story: A Woman's Legacy
2:40 - Interview Begins: Dr. Tom Karagiannis on K562 Basics
5:42 - The 1990s Gleevec Revolution: Why K562 Cells Became Essential
7:10 - The Lozio Discovery: From Patient to Immortal Cell Line
8:48 - What Makes K562 Cells Special: Continuous Growth vs Normal Cells
10:36 - Cell Culture Evolution: From Glass Pipettes to Modern Labs
12:18 - Historical Context: HeLa Cells to Cancer Virus Research
14:26 - The Philadelphia Chromosome: Understanding the Genetic Driver
17:06 - Gleevec Revolution: The First Targeted Cancer Therapy
19:48 - K562 Cell Genetics: The Near-Triploid Puzzle
21:00 - Cell Differentiation: Research Applications and Advantages
24:08 - Transferrin Receptor Research: Dr. Tom's Early Work
28:37 - K562 Cells as "Weeds": Why They're So Easy to Grow
33:08 - Evolution of Cancer Research: From Targeted Therapy to CAR-T
35:42 - Personal Research Stories: Genetic Discoveries and Insights
36:03 - Genetic Discoveries: Novel Chromosomes and Cellular Evolution
42:27 - Drug Resistance Studies: Creating Doxorubicin-Resistant Cell Lines
44:12 - Epigenetic Research: HDAC Inhibitors and Combination Therapies
49:16 - Combination Therapy Mechanisms: How HDAC Inhibitors Enhance Chemotherapy
50:40 - Drug Resistance Reality: Gleevec Limitations and Cancer Stem Cells
53:54 - K562's Continued Value: Why Genetic Drift Doesn't Diminish Research Utility
57:27 - PhD Advice
Dr. Andrew Paterson is a Senior Scientist in Genetics & Genome Biology at SickKids and a Professor at the Dalla Lana School of Public Health, University of Toronto. His work focuses on uncovering the genetic basis of diabetes and its complications.
In this episode, we discuss the real promise—and current limits—of GWAS in diabetes research, why the X chromosome is still often ignored, how datasets like GTEx and UK Biobank are shaping the future of precision medicine, and what functional follow-up really looks like. If you're curious about the path from variant to function to treatment, this one’s for you.
📖 Video Chapters:
0:00 - Highlights of the episode
2:07 - Welcome to Dr. Paterson & What Diabetes Really Is
3:11 - Monogenic, Type 1 & Type 2 — Mapping the Diabetes Family
5:11 - Life Before Insulin: Why Early Type 1 Was Fatal
6:46 - Where Each Diabetes Type Sits on the Genetic Spectrum
8:02 - HLA Breakthroughs: Early Genetic Clues to Type 1
8:45 - Childhood & Ancestry Risk: Who Gets Diabetes?
9:40 - Industrialization and the Type 2 Surge
10:55 - Do the Stats Match Patients in Clinic?
11:40 - Why Dr. Paterson Chose Diabetes & Genetics
14:02 - Genetics vs Confounding: Tracing Causal Pathways
16:17 - How Geneticists Link Variants to Disease
17:57 - 1 Billion SNPs & Linkage Disequilibrium 101
18:45 - SNP Arrays: From $1,000 to $20 Per Genome
20:07 - Whole-Genome Sequencing vs Genotyping Chips
20:58 - Cleaning Genotype Data: QC Essentials
21:49 - Regression Basics: Testing SNP–Trait Links
22:57 - Blood or Saliva? Where GWAS DNA Comes From
25:00 - The DCCT Trial & Its Landmark Design
26:44 - Conventional vs Intensive Diabetes Therapy
28:00 - C-Peptide: Residual Beta-Cell Function Insights
30:28 - Genetics, Environment & the Polygenic Reality
32:07 - Biobanks Power the Modern GWAS Boom
33:43 - Mega-Datasets: UK Biobank & Million Veteran Program
34:59 - Landmark 2010 Discovery: Gene for Glycemic Control
36:40 - Mining DCCT’s Longitudinal A1C Data with GWAS
38:44 - Diabetes-Specific Variant & DCCT’s Selective Cohort
40:00 - Conventional vs Intensive Therapy in the DCCT
41:50 - From Finger-Prick Meters to Continuous Glucose Monitors
42:48 - Breakthrough #2: COL4A3 Variant That Protects Kidneys
45:35 - Meta-GWAS Uncovers a Protective Missense Allele
47:49 - COL4A3 Minor Allele: Reduced DKD Risk
48:56 - RAST Trial & Renal Biopsy Insights
49:52 - GBM Thickness Links Genetics to Pathology
50:45 - Diabetes-Specific Gene-Environment Interaction
52:12 - Type 2 Diabetes: Power & Confounders
52:55 - Variant-to-Function Workflow: Starting the Hunt
53:45 - Tools: GWAS Catalog & GTEx for Functional Clues
55:39 - GTEx & eQTLs — Turning GWAS Hits into Gene-Expression Clues
56:46 - pQTL Goldmines: UK Biobank, deCODE & Plasma Proteomics
57:36 - From Association to Biology: How Long Does Functional Follow-Up Take?
58:49 - Modeling COL4A3 in Diabetic Mice: A Roadmap for Mechanistic Proof
60:05 - Genetics at the Top of the Drug-Discovery Funnel
61:01 - Why Genetic Targets Double a Drug’s Odds of Success
62:35 - Stop Skipping the Sex Chromosomes! X & Y in GWAS Explained
1:03:35 - Cracking the X-Chromosome Problem
1:04:30 - Imputation & Meta-Analysis Fixes
1:05:59 - Quality Concerns: Why Researchers Hesitate
1:06:55 - Polygenic Scores Need X-Linked Signals
1:07:33 - Is the Field Getting Better?
1:08:30 - Publishing Standards & Acronym Debates
1:09:12 - So… What Does This Mean for the Average Person?
1:10:53 - Precision Screening: Genetics Guides Cancer Checks
1:11:28 - From Promise to Practice: Genes in Everyday Care
1:12:03 - Career Wisdom for Aspiring Researchers
If you’ve ever analyzed sequencing data, chances are you’ve used tools developed by Phil Ewels—whether you knew it or not. He’s the creator of MultiQC, a key developer behind Nextflow and nf-core, and a major advocate for making bioinformatics workflows scalable, reproducible, and user-friendly.
In this episode, we dive into:
🔬 How MultiQC became the standard for bioinformatics quality control
⚙️ The philosophy behind nf-core and the trade-offs of workflow standardization
🤖 The role of AI in bioinformatics—will machines build pipelines for us?
🌍 The future of open-source collaboration and making workflows more accessible
If you’ve ever struggled with workflow management, questioned reproducibility, or wondered where bioinformatics is heading, this is the episode for you.
🎧 Tune in now to hear my conversation with Phil Ewels.
🤝 Connect with Phil here: https://phil.ewels.co.uk/
🐦 Tell me what you think of the episode on X: https://x.com/Mike__Kazemi
Welcome to today's episode. I'm excited to introduce our guest, Dr. Senjuti Saha, the Deputy Executive Director of the Child Health Research Foundation in Bangladesh. Dr. Saha is a trailblazer in genomic research and a passionate advocate for equitable science education. From her discovery of the chikungunya virus as a cause of pediatric meningitis to her leadership roles with the WHO and her program 'Building Scientists for Bangladesh,' Dr. Saha’s work bridges the gap between cutting-edge research and real-world impact in low- and middle-income countries. Today, we’ll dive into her journey, the challenges and opportunities in global health research, and her vision for the future. Stay tuned for an enlightening conversation.
Professor Joly is an internationally acclaimed figure in health law, intellectual property, and bioethics, leaving an enduring impact on the ethical landscape of modern medicine. With pivotal roles in the International Cancer Genome Consortium (ICGC) and the International Human Epigenome Consortium (IHEC), he has spearheaded the development and implementation of controlled access mechanisms in genomics research since 2009, influencing emerging models worldwide. With over 120 peer-reviewed publications, influential book chapters, and recognition such as the "Innovation Merit" award from the Quebec Bar, his influence extends to legal, ethical, and scientific domains. Testifying before esteemed bodies like the Council of Europe and the Canadian Senate, his expertise shapes genetic discrimination discourse. Inducted into the Canadian Academy of Health Sciences (CAHS), his current research navigates the intricate interplay of scientific knowledge, health law, and bioethics at the forefront of biotechnology and emerging health technologies.
Check out Dr. Joly's latest research here: https://tinyurl.com/25ff2u5n Connect with me here: https://twitter.com/Mike__Kazemi
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In this episode, we delve into the intricate world of the human pangenome with Cristian Groza, a Ph.D. student specializing in bioinformatics from Bourque lab at McGill University.
A Draft Human Pangenome Reference paper Connect with Cristian here Connect with me here
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Dr. Sarah Gagliano Taliun is a researcher affiliated with the Montréal Heart Institute and the Université de Montréal. She specializes in neurogenetics, complex traits, and genomics. Her research focuses on understanding genetic factors and tackling questions surrounding human health from a mechanistic and biological perspective. She employs state-of-the-art computational and bioinformatics approaches, including machine learning techniques, to study these genetic factors. Dr. Gagliano Taliun's work involves the development of predictive models that are specific to an individual's sex, contributing to personalized medicine. Using statistical and computational methods, she aims to uncover the underlying mechanisms and genetic components related to various health conditions. Her research has the potential to enhance our understanding of complex traits and advance the field of genomics.
Connect with me on Twitter: https://twitter.com/Mike__Kazemi
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Dr. John A. Morris is a Postdoctoral Scientist at the New York Genome Center, supported by a NHGRI K99 Fellowship. His work aims to understand common human genetic variation through genome editing. connect with him on Twitter or LinkedIn.
See STING-seq preprint here Check out these great Twitter threads on STING-seq here and here
Dr. Daniel Taliun is a Human Genetics Assistant Professor at McGill University. His research interests are in developing computational algorithms and software tools for analyzing genetic data combined with molecular, behavioural, imaging and environmental data.
His scope of research includes genomic and clinical data integration, web-based analytical tools and interactive visualizations, secure data sharing, distributed computational algorithms for in-house and cloud computing computational platforms, analysis of rare genetic variations across diverse populations, and gene-disease associations.
Connect with me on Twitter: https://twitter.com/Mike__Kazemi This podcast is produced in collaboration with CKUT radio: https://ckut.ca/
Dr. Raquel Cuella Martin joined the Department of Human Genetics and the Canada Excellence Research Chair in Genomic Medicine as an assistant professor in August 2022.
Dr. Martin's current research employs large-scale precision genome editing to investigate the DNA damage response and its connection to human disorders. Her lab aims to integrate DNA repair and checkpoint control activities to prevent tumorigenesis and preserve cellular homeostasis. The lab also explores how precision genome editing can help understand disease-associated genetic variation and advance intelligent drug design.
Connect with her on Twitter: https://twitter.com/raquel_cuella
Connect with me on Twitter: https://twitter.com/Mike__Kazemi
This podcast is produced in collaboration with CKUT radio: https://ckut.ca/