This week on The Genetics Podcast, Patrick is joined by Raghib Ali, CEO, CMO, and Principal Investigator of Our Future Health UK. As a clinical epidemiologist with a passion for reducing health inequalities, Raghib offers fresh insights into the priorities, challenges, and transformative impact of the groundbreaking genomics initiative, Our Future Health. 

Show Notes: 

0:00 Intro to The Genetics Podcast

01:00 Welcome to Raghib and background on Our Future Health (OFH)

03:57 Diseases that are a priority for OFH or are likely to benefit from its impact

06:07 Challenges and opportunities for implementing change in the National Health Service (NHS), a partner of OFH, based on study findings

09:20 Factors that contributed to the rapid recruitment of participants to OFH

14:12 Efforts to ensure diversity of OFH participants and facilitate accessibility for all

16:35 Why OFH chose to use arrays for genomic profiling

18:57 Navigating the obstacles and opportunities in public and private partners

22:28 Strengths and weaknesses of the medical record system in the UK

25:54 Efforts to rapidly provide results from OFH and integrating other datasets and techniques in the future

28:43 Raghib’s unique educational and training journey 

31:49 The importance of evaluating components beyond genetics for a full picture of health

33:28 Aims and findings of the first prospective cohort study in the UAE

35:26 The potential contribution of epigenetic inheritance to disease risk 

37:43 How Raghib overcame adversity early in life

40:56 Closing remarks 

Find out more

• Our Future Health (https://ourfuturehealth.org.uk/)

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, we’re celebrating Rare Disease Day with a very special episode. Patrick is joined by clinical nephrologist Anthony Bleyer and geneticist Stan Kmoch to discuss how their decade-long international collaboration has uncovered genetic mutations in families with rare inherited kidney diseases – including Patrick’s.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Anthony and Stan

02:05 The origin story for Anthony and Stan’s long-distance collaboration

06:55 Stan’s background in metabolic disorders and sequencing techniques

11:09 Common genetic culprits and barriers to identifying mutations that cause kidney disease

14:01 Background and findings from Anthony and Stan’s ApoA4 study

23:54 Potential therapeutic avenues based on the ApoA4 study

26:49 Current and future focuses for characterizing diseases in families

30:42 Working with collaborators internationally to access large databases and registries

33:05 Innovative transplant methods, including genetically-modified pig kidneys

36:36 Closing remarks and a heartfelt thank you to researchers and families driving rare disease research

Find out more

• Latest study: https://doi.org/10.1016/j.kint.2023.11.021

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Michelle Werner, CEO at Alltrna and CEO/Partner at Flagship Pioneering. They discuss Alltrna’s promising findings from its first preclinical study on using tRNA to rescue stop codon disease, the strategic use of basket trials, and more!

Show Notes: 

0:00 Intro to The Genetics Podcast

01:00 Welcome to Michelle

02:13 Overview of Alltrna’s aims and the advantages of using tRNA to tackle stop codon disease

5:27 Using basket trials for genetic diseases

08:03 Highlights from Alltrna’s first preclinical study using tRNA to restore protein production to clinically meaningful levels in methylmalonic acidemia (MMA) and phenylketonuria (PKU)

14:02 Considerations in delivery techniques and Alltrna’s use of nanoparticles

19:22 Stability of tRNA and how engineered tRNAs are recognized in vivo 

23:12 Strategic design of basket trials and diseases that are covered

26:16 Adaptive trial design in the rare genetic disease setting

28:15 Michelle’s experience with regulatory organizations on new approaches to trial design

32:14 Insights from spearheading Alltrna and Flagship Pioneering’s innovative approaches 

37:26 Michelle’s lessons from working in big pharma versus a small biotech start-up

40:50 Closing remarks and a call for collaborators

Find out more

• Alltrna (https://www.alltrna.com/)

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

On this week’s episode of The Genetics Podcast, we’re joined by Jocelynn Pearl, Director of Cancer Cell Therapy at the TAM Center, host of the Lady Scientist Podcast and Co-Founder of LabDAO. Patrick and Jocelynn discuss her move to Mexico to help accelerate the development of new cancer therapies, harnessing the power and potential of decentralized science, and overcoming sky-high gene therapy costs to increase accessibility for patients.

Show Notes: 

0:00Intro to The Genetics Podcast

01:00Welcome to Jocelynn

02:03 Jocelynn’s past work at The Institute for Systems Biology 

04:55 How Jocelynn approached her transition to biotech from the world of academia

10:14 Exploring decentralized science, including how it works and Jocelynn’s involvement to date

15:54 What a Decentralized Autonomous Organisation (DAO) is and how this type of organizational structure supports scientific development

22:45 The “fast grant” surge and other non-traditional funding methods

28:00 Hosting the Lady Scientist Podcast and some of Jocelynn’s favorite moments

32:43 Jocelynn’s move to Mexico to serve as Director of Cancer Cell Therapy at the TAM Center

36:12 The biggest differences between building out drug development programs in Mexico and the US

38:31 Regulatory differences between countries in the context of stem cell therapies

42:48 The advantages for cancer therapeutic development in Jocelynn’s current environment

46:20Driving down the costs of gene therapies and the impact on accessibility  

48:09 Closing remarks

Find out more

LabDAO:https://www.lab.bio/ 

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Summary: 

This week on The Genetics Podcast, Patrick is joined by Eric Adler, Chief Medical Officer and Head of Research at Lexeo Therapeutics and Professor of Medicine at University of California San Diego. Eric shares his experience with genetic cardiomyopathy and his work on gene therapy for Danon disease, drawing from both clinical and research perspectives. Additionally, he explores the evolution of the field and the broader challenges faced by cardiovascular patients.

Show Notes: 

0:00 Intro to The Genetics Podcast

01:00 Welcome to Eric and his efforts in cardiomyopathy at the bench and bedside

03:32 How modeling genetic diseases using pluripotent stem cells lead Eric to studying Danon disease 

04:50 Pivoting from basic to translational research using adeno-associated viruses (AAV)-based gene therapy

07:58 Uncovering genetic cardiomyopathies that were misdiagnosed as idiopathic cardiomyopathy

09:55 Treatment, screening, and penetrance of Danon disease

12:30 Recent successes and remaining challenges in cardiovascular disease

19:47 Battling distrust in the medical profession

21:55 Preventative therapy using APOE2 for patients at risk of early Alzheimer’s

25:15 Motivations behind and advantages of Eric’s patient-centered approach to therapeutics

27:24 Balancing regulatory requirements for protocols versus patient needs

29:49 The importance of committed clinical partners for successful trial execution

36:08 Eric’s passion for cooking and how he won a cooking competition

39:02 Closing remarks and Lexeo Therapeutics’ aims for 2025

Find out more

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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Versha Pleasant, Clinical Assistant Professor in the Department of Obstetrics and Gynecology, University of Michigan and Director of the Cancer Genetics and Breast Health Clinic at Von Voigtlander Women’s Hospital. They discuss ongoing disparities in healthcare, in particular why black women in the US have a 40% higher chance of dying from breast cancer than white women, the impact of the US Educate Act on equality, diversity and inclusion education, and much more.

00:00:00 – Intro to The Genetics Podcast

00:01:52 – Welcome to Versha

00:03:22 – How black women have a 40% higher chance of mortality from breast cancer than white women, and the biggest drivers of this disparity

00:07:09 – Multifaceted approaches to addressing disparities

00:09:10 – Racial health duplicity and increasing access to genetic testing and mammography for black women

00:13:51 – The challenges of using precision medicine to stratify risk in black communities and historical harms in US medical research

00:14:29 – How to design for inclusive studies that effectively represent communities of colour

00:16:13 – Considering universal genetic testing and counseling for black women

00:21:24 – The logistics of making universal testing a reality, and the importance of community education and trust building

00:27:18 – What Versha is focused on next and the big topics she wants to tackle

00:33:24 – The role of community education and diversifying modes of communication for knowledge sharing

00:34:36 – Versha’s perspectives on the US Educate Act and the impact it could have on what doctors of the future are taught

00:40:52 – Versha’s advice to people who would like to pursue a similar career in medicine

00:43:28 – Where Patrick sees genetics evolving in the next ten years and his vision for the future of The Genetics Podcast

00:47:39 – Closing remarks

Find out more

Universal Genetic Counseling and Testing for Black Women: A Risk-Stratified Approach to Addressing Breast Cancer Disparities: https://www.clinical-breast-cancer.com/article/S1526-8209(24)00338-0/fulltext 

Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link