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.

#genetics #blood #platelets

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.