Celebrating academic success and overcoming obstacles

Congratulations to Yasmine Arafa (she/hers), a CIRM Bridges Student Intern at UC Davis Institute for Regenerative Cures! She recently graduated from California State University-Sacramento, officially concluding her Master’s degree and Fulbright Association journey. She conducted research with the aim of developing new therapeutic approaches for rare diseases.

Yasmine says, “I have finally passed my thesis defense and am now a Master‘s degree holder. People in grad school tend to not celebrate their achievements as much, but I chose to celebrate mine.”

“As a graduate student who started their degree in 2020, it has been a rough journey for me. Coming to a new country on my own, away from my family and loved ones, during a pandemic, has been quite the challenge. I‘m proud of myself and of this achievement, because I know the immense amount of academic and mental effort I had to put in to get to this point. To all graduate students out there, don‘t forget to celebrate your success!”

Congrats, Yasmine! She joins 1,663 CIRM Bridges alumni who are helping build the next generation of scientists and meet CIRM’s mission to #AccelerateWorldClassScience here in California for the world. 

To learn more about CIRM’s internship programs, visit our website.

Stem Cell Agency Board Invests in 19 Discovery Research Programs Targeting Cancers, Heart Disease and Other Disorders

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Dr. Judy Shizuru, Stanford University

While stem cell and gene therapy research has advanced dramatically in recent years, there are still many unknowns and many questions remaining about how best to use these approaches in developing therapies. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) today approved investing almost $25 million in 19 projects in early stage or Discovery research.

The awards are from CIRM’s DISC2 Quest program, which supports  the discovery of promising new stem cell-based and gene therapy technologies that could be translated to enable broad use and ultimately, improve patient care.

“Every therapy that helps save lives or change lives begins with a researcher asking a simple question, “What if?”, says Dr. Maria T. Millan, the President and CEO of CIRM. “Our Quest awards reflect the need to keep supporting early stage research, to gain a deeper understanding of stem cells work and how we can best tap into that potential to advance the field.”

Dr. Judy Shizuru at Stanford University was awarded $1.34 million to develop a safer, less-toxic form of bone marrow or hematopoietic stem cell transplant (HCT). HCT is the only proven cure for many forms of blood disorders that affect people of all ages, sexes, and races worldwide. However, current methods involve the use of chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. This approach is toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.

Dr. Shizuru proposes developing an antibody that can direct the patient’s own immune cells to kill diseased blood stem cells. This would make stem cell transplant safer and more effective for the treatment of many life-threatening blood disorders, and more accessible for people in rural or remote parts of the country.

Lili Yang UCLA Broad Stem Cell Research Center: Photo courtesy Reed Hutchinson PhotoGraphics

Dr. Lili Yang at UCLA was awarded $1.4 million to develop an off-the-shelf cell therapy for ovarian cancer, which causes more deaths than any other cancer of the female reproductive system.

Dr. Yang is using immune system cells, called invariant natural killer T cells (iNKT) to attack cancer cells. However, these iNKT cells are only found in small numbers in the blood so current approaches involve taking those cells from the patient and, in the lab, modifying them to increase their numbers and strength before transplanting them back into the patient. This is both time consuming and expensive, and the patient’s own iNKT cells may have been damaged by the cancer, reducing the likelihood of success.

In this new study Dr. Yang will use healthy donor cord blood cells and, through genetic engineering, turn them into the specific form of iNKT cell therapy targeting ovarian cancer. This DISC2 award will support the development of these cells and do the necessary testing and studies to advance it to the translational stage.

Timothy Hoey and Tenaya Therapeutics Inc. have been awarded $1.2 million to test a gene therapy approach to replace heart cells damaged by a heart attack.

Heart disease is the leading cause of death in the U.S. with the highest incidence among African Americans. It’s caused by damage or death of functional heart muscle cells, usually due to heart attack. Because these heart muscle cells are unable to regenerate the damage is permanent. Dr. Hoey’s team is developing a gene therapy that can be injected into patients and turn their cardiac fibroblasts, cells that can contribute to scar tissue, into functioning heart muscle cells, replacing those damaged by the heart attack.

The full list of DISC2 Quest awards is:

APPLICATION NUMBERTITLE OF PROGRAMPRINCIPAL INVESTIGATORAMOUNT
  DISC2-13400  Targeted Immunotherapy-Based Blood Stem Cell Transplantation    Judy Shizuru, Stanford Universtiy  $1,341,910    
  DISC2-13505  Combating Ovarian Cancer Using Stem Cell-Engineered Off-The-Shelf CAR-iNKT Cells    Lili Yang, UCLA  $1,404,000
  DISC2-13515  A treatment for Rett syndrome using glial-restricted
neural progenitor cells  
  Alysson Muotri, UC San Diego  $1,402,240    
  DISC2-13454  Targeting pancreatic cancer stem cells with DDR1 antibodies.    Michael Karin, UC San Diego  $1,425,600  
  DISC2-13483  Enabling non-genetic activity-driven maturation of iPSC-derived neurons    Alex Savtchenko, Nanotools Bioscience  $675,000
  DISC2-13405  Hematopoietic Stem Cell Gene Therapy for Alpha
Thalassemia  
  Don Kohn, UCLA    $1,323,007  
    DISC2-13507  CAR T cells targeting abnormal N-glycans for the
treatment of refractory/metastatic solid cancers  
  Michael Demetriou, UC Irvine  $1,414,800  
  DISC2-13463  Drug Development of Inhibitors of Inflammation Using
Human iPSC-Derived Microglia (hiMG)  
  Stuart Lipton, Scripps Research Inst.  $1,658,123  
  DISC2-13390  Cardiac Reprogramming Gene Therapy for Post-Myocardial Infarction Heart Failure    Timothy Hoey, Tenaya Therapeutics  $1,215,000  
  DISC2-13417  AAV-dCas9 Epigenetic Editing for CDKL5 Deficiency Disorder    Kyle Fink, UC Davis  $1,429,378  
  DISC2-13415  Defining the Optimal Gene Therapy Approach of
Human Hematopoietic Stem Cells for the Treatment of
Dedicator of Cytokinesis 8 (DOCK8) Deficiency  
  Caroline Kuo, UCLA  $1,386,232  
  DISC2-13498  Bioengineering human stem cell-derived beta cell
organoids to monitor cell health in real time and improve therapeutic outcomes in patients  
  Katy Digovich, Minutia, Inc.  $1,198,550  
  DISC2-13469  Novel antisense therapy to treat genetic forms of
neurodevelopmental disease.  
  Joseph Gleeson, UC San Diego  $1,180,654  
  DISC2-13428  Therapeutics to overcome the differentiation roadblock in Myelodysplastic Syndrome (MDS)    Michael Bollong, Scripps Research Inst.  $1,244,160  
  DISC2-13456  Novel methods to eliminate cancer stem cells    Dinesh Rao, UCLA  $1,384,347  
  DISC2-13441  A new precision medicine based iPSC-derived model to study personalized intestinal fibrosis treatments in
pediatric patients with Crohn’s diseas  
  Robert Barrett Cedars-Sinai  $776,340
  DISC2-13512  Modified RNA-Based Gene Therapy for Cardiac
Regeneration Through Cardiomyocyte Proliferation
  Deepak Srivastava, Gladstone Institutes  $1,565,784
  DISC2-13510  An hematopoietic stem-cell-based approach to treat HIV employing CAR-T cells and anti-HIV broadly
neutralizing antibodies  
  Brian Lawson, The Scintillon Institute  $1,143,600  
  DISC2-13475  Developing gene therapy for dominant optic atrophy using human pluripotent stem cell-derived retinal organoid disease model    Xian-Jie Yang, UCLA  $1,345,691  

Stem cells explained in different languages

Science is hard. Explaining complex science to non-scientists is SUPER hard. But explaining science to non-native English speakers presents a whole new set of challenges.  

I would know. I’m a first-generation immigrant whose highly-educated parents arrived in their new home—the United States—a tad too late to become fluent in its native tongue. I’ve also had the unique experience of participating in a clinical trial using stem cells—a topic which my family still has trouble grasping.  

I still remember the day of my accident, which left me paralyzed from the chest down. My mother came into my room to cheerfully tell me that there was “something” that would “help me walk” again. Those “something” were human embryonic stem cells. The “help me walk” part was doctors simply explaining the potential of the treatment. In her frazzled mind, she could hardly understand Farsi, much less English. Being told that I was a candidate to participate in a stem cell trial somehow translated into being cured.

And she kept looking for the magic bullet. Countless internet searches revealed all sorts of clinics and wellness centers that offered a cure to just about any disease imaginable. My mom wondered, “Were these the same stem cells from my daughter’s trial? Maybe they are even better since they are curing so many folks!”

I tried my best to explain but there was always something missing in translation. I found that troubling. The language barrier made it so difficult to make informed decisions. I couldn’t imagine being a non-native English speaker and learning about such a complicated matter in a language I hadn’t yet mastered.

After all, stem cells are a topic that concerns the people of the world, not just certain countries or certain people speaking only in certain languages.

Dr. Paul Knoepfler would know. And not just because the statement comes straight from him. Paul is a stem cell scientist at UC Davis (full disclosure, we have funded some of his work). His blog, The Niche, is one of the longest-running blogs about regenerative medicine and an especially great resource for those without a science background.

More importantly, in 2021 Dr. Knoepfler launched SCOPE, an outreach effort to make available on the internet a basic page of facts about stem cells in as many languages as possible. What started with “Stem Cells in Spanish” has quickly transformed into a stem cell white paper now available in 35 different languages!

Naturally, I wasted no time and sent the Farsi version to my parents and the French one to my francophone mother-in-law. And it isn’t just me who is finding this information useful. Dr. Knoepfler says, “SCOPE has been a big hit and as the number of languages has grown, the number of page views of my white paper ‘What are stem cells?’ in languages besides English has skyrocketed. For example, just our Stem Cells in Spanish page has received over 680,000 views as of the first half of 2021, while our Indonesian page has over 300,000 views and our Arabic page has a quarter of a million. We are getting readers from all over the world who appreciate reading about stem cells in their own languages.”

To learn more about this initiative, visit Dr. Knoepfler’s blog.

The power of the patient advocate: how a quick visit led to an $11M grant to fund a clinical trial

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Members of NFOSD visiting UC Davis in 2013

At the California Institute for Regenerative Medicine (CIRM) we are fortunate in having enough money to fund the most promising research to be tested in a clinical trial. Those are expensive projects, often costing tens of millions of dollars. But sometimes the projects that come to our Board start out years before in much more humble circumstances, raising money through patient advocates, tapping into the commitment and ingenuity of those affected by a disease, to help advance the search for a treatment.

That was definitely the case with a program the CIRM Board voted to approve yesterday, investing more than $11 million dollars to fund a Phase 2 clinical trial testing a cell therapy for dysphagia. That’s a debilitating condition that affects many people treated for head and neck cancer.

Patients with head and neck cancer often undergo surgery and/or radiation to remove the tumors. As a result, they may develop problems swallowing and this can lead to serious complications such as malnutrition, dehydration, social isolation, or a dependence on using a feeding tube. Patients may also inhale food or liquids into their lungs causing infections, pneumonia and death. The only effective therapy is a total laryngectomy where the larynx or voice box is removed, leaving the person unable to speak.

Dr. Peter Belafsky and his team at the University of California at Davis are developing a therapeutic approach using Autologous Muscle Derived Progenitor Cells (AMDC), cells derived from a biopsy of the patient’s own muscle, elsewhere in the body. Those AMDCs are injected into the tongue of the patient, where they fuse with existing muscle fibers to increase tongue strength and ability to swallow.

The $11,015,936 that Dr. Belafsky is getting from CIRM will enable them to test this approach in patients. But without grass roots support the program might never have made it this far.

Ed Steger is a long-term survivor of head and neck cancer, he’s also the President of the National Foundation of Swallowing Disorders (NFOSD). In 2007, after being treated for his cancer, Ed developed a severe swallowing disorder. It helped motivate him to push for better treatment options.

In 2013, a dozen swallowing disorder patients visited UC Davis to learn how stem cells might help people with dysphagia. (You can read about that visit here). Ed says: “We were beyond thrilled with the possibilities and drawing on patients and other UCD contacts our foundation raised enough funds to support a small UCD clinical trial under the guidance of Dr. Belafsky in mouse models that demonstrated these possibilities.”

A few years later that small funding by patients and their family members grew into a well-funded Phase I/II human clinical trial. Ed says the data that trial produced is helping advance the search for treatments.

“Skipping forward to the present, this has now blossomed into an additional $11 million grant, from CIRM, to continue the work that could be a game changer for millions of Americans who suffer annually from oral phase dysphagia. My hat is off to all those that have made this possible… the donors, patient advocates, and the dedicated committed researchers and physicians who are performing this promising and innovative research.”

Our hats are off to them too. Their efforts are making what once might have seemed impossible, a real possibility.

Google eases ban on ads for stem cell therapies

What started out as an effort by Google to crack down on predatory stem cell clinics advertising bogus therapies seems to be getting diluted. Now the concern is whether that will make it easier for these clinics to lure unsuspecting patients to pay good money for bad treatments?

A little background might help here. For years Google placed no restrictions on ads by clinics that claimed their stem cell “therapies” could cure or treat all manner of ailments. Then in September of 2019 Google changed its policy and announced it was going to restrict advertisements for stem cell clinics offering unproven, cellular and gene therapies.

This new policy was welcomed by people like Dr. Paul Knoepfler, a stem cell scientist at UC Davis and longtime critic of these clinics. In his blog, The Niche, he said it was great news:

“Google Ads for stem cell clinics have definitely driven hundreds if not thousands of customers to unproven stem cell clinics. It’s very likely that many of the patients who have ended up in the hospital due to bad outcomes from clinic injections first went to those firms because of Google ads. These ads and certain particularly risky clinics also are a real threat to the legitimate stem cell and gene therapy fields.”

Now the search-engine giant seems to be adjusting that policy. Google says that starting July 11 it will permit ads for stem cell therapies approved by the US Food and Drug Administration (FDA). That’s fine. Anything that has gone through the FDA’s rigorous approval process deserves to be allowed to advertise.

The real concern lies with another adjustment to the policy where Google says it will allow companies to post ads as long as they are “exclusively educational or informational in nature, regardless of regulatory approval status.” The problem is, Google doesn’t define what constitutes “educational or informational”. That leaves the door open for these clinics to say pretty much anything they want and claim it meets the new guidelines.

To highlight that point Gizmodo did a quick search on Google using the phrase “stem cells for neuropathy” and quickly came up with a series of ads that are offering “therapies” clearly not approved by the FDA. One ad claimed it was “FDA registered”, a meaningless phrase but one clearly designed to add an air of authenticity to whatever remedy they were peddling.

The intent behind Google’s change of policy is clearly good, to allow companies offering FDA-approved therapies to advertise. However, the outcome may not be quite so worthy, and might once again put patients at risk of being tricked into trying “therapies” that will almost certainly not do them any good, and might even put them in harm’s way.

It’s hard to be modest when people keep telling you how good you are

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I have a confession. Deep down I’m shallow. So when something I am part of is acknowledged as one of the best, I delight in it (my fellow bloggers Katie and Esteban also delight in it, I am just more shameless about letting everyone know.)

And that is just what happened with this blog, The Stem Cellar. We have been named as one of the “22 best biology and stem cell blogs of 2022”. And not just by anyone. We were honored by Dr. Paul Knoepfler, a stem cell scientist, avid blogger and all-round renaissance man (full disclosure, Paul is a recipient of CIRM funding but that has nothing to do with this award. Obviously.)

We are particularly honored to be on the list because Paul includes some heavy hitters including The Signals Blog, a site that he describes this way:

“This one from our friends in Canada is fantastic. They literally have dozens of authors, which is probably the most of any stem cell-related website, and their articles include many interesting angles. They post really often too. I might rank Signal and The Stem Cellar as tied for best stem cell blog in 2021.”

Now I’m really blushing.

Other highly regarded blogs are EuroStemCell, the Mayo Clinic Regenerative Medicine Blog and Stem Cell Battles (by Don Reed, a good friend of CIRM’s)

Another one of the 22 is David Jensen’s California Stem Cell report which is dedicated to covering the work of, you guessed it, CIRM. So, not only are we great bloggers, we are apparently great to blog about. 

As a further demonstration of my modesty I wanted to point out that Paul regularly produces ‘best of’ lists, including his recent “50 influencers on stem cells on Twitter to follow” which we were also on.

Stem cell agency invests in therapy using killer cells to target colorectal, breast and ovarian cancers

While there have been some encouraging advances in treating cancer in recent decades, there are still many cancers that either resist treatment or recur after treatment. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved investing in a therapy targeting some of these hard-to-treat tumors.

BioEclipse Therapeutics Inc. was awarded nearly $8M to test a therapy using immune cells loaded with a cancer-killing virus that targets cancer tissue but spares healthy tissue.

This is the 78th clinical trial funded directly by the Stem Cell Agency.

BioEclipse combines two approaches—an immune cell called a cytokine-induced killer (CIK) cell and a virus engineered to kill cancer cells called an oncolytic virus (OV)—to create what they call “a multi-mechanistic, targeted treatment.”

They will use the patient’s own immune cells and, in the lab, combine them with the OV. The cell/virus combination will then be administered back to the patient. The job of the CIK cells is to carry the virus to the tumors. The virus is designed to specifically attack and kill tumors and stimulate the patient’s immune system to attack the tumor cells. The goal is to eradicate the primary tumor and prevent relapse and recurrence.

“With the intent to develop this treatment for chemotherapy-resistant or refractory solid tumors—including colorectal cancer, triple negative breast cancer, ovarian cancer, gastric cancer, hepatocellular carcinoma, and osteosarcoma—it addresses a significant unmet medical need in fatal conditions for which there are limited treatment options,” says Dr. Maria T. Millan, President and CEO of CIRM.  

The CIRM Board also approved more than $18 million in funding four projects under the Translation Projects program. The goal of this program is to support promising regenerative medicine (stem cell-based or gene therapy) projects that accelerate completion of translational stage activities necessary for advancement to clinical study or broad end use.

The awards went to:

ApplicationTitleInstitutionAward Amount
TRAN1-133442Optogenetic therapy for treating retinitis pigmentosa and
other inherited retinal diseases  
  Paul Bresge Ray Therapeutics Inc.  $3,999,553  
TRAN3-13332Living Synthetic Vascular Grafts with Renewable Endothelium    Aijun Wang UC Davis  $3,112,567    
TRAN1-13370Next generation affinity-tuned CAR for prostate cancer    Preet Chaudhary University of Southern California  $5,805,144  
TRAN1-3345Autologous MPO Knock-Out Hematopoietic Stem and
Progenitor Cells for Pulmonary Arterial Hypertension  
  Don Kohn UC Los Angeles  $5,207,434  

Making the list of people to follow

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If you are walking down the street on a dark night, being followed is not necessarily something you want. But if you are online, having someone follow you is almost always a positive thing. And when that person is Dr. Paul Knoepfler it’s most definitely a plus.

Paul is a stem cell scientist at UC Davis (full disclosure, we have funded some of his work). He’s also one of the longest-running and most active bloggers about regenerative medicine and an ever-present presence on Twitter. His blog is always a great read and, for those of us without a science background, easy to follow and understand.

Dr. Paul Knoepfler, UC Davis: Photo courtesy UC Davis

That’s why it’s quite an honor that Paul has listed the California Institute for Regenerative Medicine’s as one of the 50 Influencers on stem cells to follow on Twitter.

Paul says this does not necessarily mean the most influential in the field of research because many researchers – such as Nobel Prize winner Dr. Shinya Yamanaka – don’t use Twitter. He says in making the list he looked for a few key elements.

“I particularly appreciate those accounts that include a mix of info, news, and opinion with original content or opinions of their own too.

“I emphasized inclusion of those accounts who regularly tweet. Also, I aimed for a good mixture of accounts across the globe, not just in the U.S. I also included stem cell policy researchers and bioethicists.”

“I picked this list of 50… for 2022 based simply on my impressions of their influence or because they do interesting tweets and/or have a fresh perspective on things, not strictly based on metrics.”

Whatever the reason, we’re delighted, and honored to be on Paul’s list.

And if you would like to see why we made the ’50 to Follow list’, then follow us on Twitter

UC Davis Health researchers aim to use CAR T cells for HIV cure

Dr. Abedi (right) in the lab at UC Davis Health. He and his team of researchers have launched a study looking to identify a potential cure for HIV. Photo Courtesy of UC Davis Health.

Worldwide, almost 38 million people are living with HIV—the virus that can lead to AIDS— and it’s estimated that 75% of them receive antiviral treatment to keep the virus in check. In California, 150,000 people live with HIV and 68% of these individuals are virally suppressed due to treatment.  

To fight this virus, UC Davis Health researchers—with funding from a CIRM grant—have launched a study looking to identify a potential cure for HIV. Using immunotherapy, researchers will take a patient’s own white blood cells, called T-cells, and modify them so that they can identify and target HIV cells to control the virus without medication. 

Targeting HIV with CAR T cells

“For this study we will educate the cells by inserting a gene to target cells that have been infected by the HIV virus,” explained Mehrdad Abedi, professor of internal medicine, hematology and oncology and the principal investigator of the study. “The idea is these modified cells will attach to the HIV-infected cells and destroy the cells that are infected while also stopping the infected cells’ ability to replicate.” 

Modified T-cells, known as CAR T cells, are an FDA-approved treatment for different forms of cancer including acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma. With cancer, the immune system often fails to deploy T-cells right away or at all. When it does, the attack is ineffective. CAR T-cell immunotherapy changes these collected T-cells to produce chimeric antigen receptors (or CARs) that adhere to tumors to destroy them. 

Study seeking HIV patients

For the study, UC Davis Health researchers are working to identify and recruit HIV-positive patients between the ages of 18 and 65 who have had an undetectable HIV viral load for the 12 months and have been on continuous antiretroviral therapy for at least 12 months.  

Patients also need to be willing to pause their antiretroviral therapy as part of the study. 

“While it is exciting, the study will require a lot of dedication from the patient because of the time commitment involved and the necessary steps required,” said Paolo Troia-Cancio, a clinical professor of medicine with the infectious disease division with over 20 years of experience treating HIV and co-investigator on the CAR T cell study.   

The search for an HIV cure 

Three patients have been cured of HIV using bone marrow transplants, including a woman in New York who received a cord blood stem cell transplant. She received a bone marrow transplant using umbilical cord blood donor cells that bore a mutation that makes them resistant to HIV infection to treat her leukemia. 

There have also been two previous cases involving an HIV cure following allogeneic bone marrow transplants. Both patients had leukemia and received bone marrow transplants from donors who carried the same mutation that blocks HIV infection.  

“While these stories provide inspiration and hope to finding a cure for HIV, a bone marrow transplant is not a realistic option for most patients,” said Abedi. “Such transplants are highly invasive and risky, so they are generally offered only to people with cancer who have exhausted all other options.” 

Abedi and his fellow researchers see this study as a potential road map to finding a cure for HIV.  

The California Institute for Regenerative Medicine (CIRM) has funded earlier work by Dr. Abedi and his team in trying to develop a therapy to help people with HIV who also have lymphoma.  

To read the source article about this CIRM-funded study, click here

Promoting stem cell therapies, racial justice and fish breeding

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Jan Nolta, PhD, in her lab at UC Davis; Photo courtesy UC Davis

Working at CIRM you get to meet many remarkable people and Dr. Jan Nolta certainly falls into that category. Jan is the Director of the Stem Cell Program at UC Davis School of Medicine. She also directs the Institute for Regenerative Cures and is scientific director of both the Good Manufacturing Practice clean room facility at UC Davis and the California Umbilical Cord Blood Collection Program.

As if that wasn’t enough Jan is part of the team helping guide UC Davis’ efforts to expand its commitment to diversity, equity and inclusion using a variety of methods including telemedicine, to reach out into rural and remote communities.

She is on the Board of several enterprises, is the editor of the journal Stem Cells and, in her copious spare time, has dozens of aquariums and is helping save endangered species.

So, it’s no wonder we wanted to chat to her about her work and find out what makes her tick. Oh, and what rock bands she really likes. You might be surprised!

That’s why Jan is the guest on the latest edition of our podcast ‘Talking ‘Bout (re)Generation’.

I hope you enjoy it.