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What Is This Wizardry?

December 11, 2023
Juliana Perez Botero, MD, (@JuliPerezBot)
Versiti and Medical College of Wisconsin, Milwaukee, WI

“Teamwork, commitment, humility, and a problem-solving mindset.” These are the words of wisdom from Pamela Ting, PhD, associate director of hematology at Novartis Pharmaceuticals, when asked what it takes to advance science. Her team’s groundbreaking discovery, “Targeted Degradation of the Wiz Transcription Factor for Gamma Globin De-Repression,” shared at yesterday’s Plenary Scientific Session, falls nothing short of a magical manipulation potion. Breaking the paradigm that transcription factors cannot be pharmacologically targeted, they have discovered and optimized compounds able to de-repress fetal hemoglobin (HbF).  

The journey of scientific discovery is full of twists, turns, and revelations. “We were all pleasantly surprised when we identified dWIZ-1 in the phenotypic screen — a single molecule with the phenotype that we had been searching for a long time, which produced robust fetal hemoglobin induction with no undesirable effects on cell proliferation and differentiation,” said Dr. Ting about an event that defined the course of their research. The ability to pivot and change strategy is also key: “We had previously screened our traditional chemical library of over 2M compounds without any traction. And so, although we went into the screen with a new hypothesis — that a focused library of chemical matter biased for targeting transcription factors might give us new leverage to find molecules that could re-activate fetal hemoglobin — we were all still surprised and excited when we got the hit. We've been chasing that hit down since.”  

When you work with passion and purpose, enjoy the process as much as the outcome, and surround yourself with a group of like-minded people, you don’t need a magic wand. “[It has been] an incredibly humbling and empowering experience to be a part of a team where we each bring the skills that we have, and where we acknowledge that we don't always know the answers or see the path on our own, but we will figure it out and build it together,” said Dr. Ting. She added, “I so admire my colleagues and am so inspired by how they bring their best every day. Some days our best is an innovative scientific breakthrough, some days it's saying, ‘I don't agree with you, but I will keep listening’, and some days it's simply saying, ‘It didn't pan out today, but we will come back tomorrow and try again.’” 

A milestone may be the end of one road, but it's also the beginning of another. What is Dr. Ting looking forward to? “I’m excited about developing the knowledge and know-how around targeted protein degradation. I'm excited about how our research lays a path toward investigational new medicines for sickle cell disease (SCD) patients. I'm also deeply honored and grateful to be a part of the global SCD scientific community. It is inspiring to reflect on the foundational work that others have done to build our knowledge of hemoglobin switching and SCD, and incredibly cool to see the field evolve further with new technologies such as CRISPR-Cas9 and targeted protein degradation.” 

On the challenges in the path her career has taken, Dr. Ting shared, “I feel incredibly privileged to get to do the work I do. This quote by Jennifer Heemstra, PhD, chair and professor of chemistry at Washington University in St. Louis, resonates with me: ‘Sometimes the difference between a challenge that can crush you and a challenge that will energize you is the people walking through it with you.’ Because of the people around me, I don't feel the challenges — only the collective support, determination and hope.” 

 

Dr. Perez Botero indicated no relevant conflicts of interest.  

 

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