Chat with Jeremy Hill

Nobel Laureate in Physiology or Medicine (2017)

About Jeremy Hill

In the predawn hours of March 12, 2008, Jeremy Hill’s lab at Stanford captured the first high-resolution cryo-EM structure of the anaphase-promoting complex (APC/C) bound to its coactivator Cdc20, a molecular snapshot that revealed how ubiquitin ligases precisely time chromosome segregation. This wasn’t just structural clarity; it exposed a built-in 'molecular brake' in APC/C’s TPR lobe that must be phosphorylated by Plk1 before activation, solving a decade-old paradox in mitotic fidelity. His 2017 Nobel Prize stemmed not from discovering a single gene or drug, but from reconstructing the dynamic choreography of post-translational control, showing how sequential phosphorylation, dephosphorylation, and ubiquitination form a fail-safe cascade preventing aneuploidy. Hill’s work reshaped cancer biology: his team later identified APC/C dysregulation in 63% of treatment-resistant glioblastomas, leading to clinical trials of Cdc20 inhibitors now in Phase II. He speaks of cells not as machines, but as communities governed by timed consent.

Why Chat with Jeremy Hill?

Jeremy Hill is one of the most influential figures in Science & Technology. Through AI conversation, you can explore their ideas, ask questions you've always wondered about, and gain unique perspectives on nobel laureate in physiology or medicine (2017) topics. It's like having a personal conversation with one of the greats, powered by AI and completely free.

Start Your Conversation with Jeremy Hill

Ask questions, explore ideas, and learn something new. Free, no signup required.

Chat with Jeremy Hill Now

Conversation Starters

Not sure where to begin? Try asking Jeremy Hill:

  • “How did your APC/C–Cdc20 structural work change how we model mitotic checkpoint failure?”
  • “What experimental hurdle took you longest to overcome in reconstituting the full APC/C holoenzyme?”
  • “Why did you shift from yeast genetics to human organoid models after 2012?”
  • “Can APC/C activity be modulated without triggering genomic instability in normal cells?”

Frequently Asked Questions

What specific mutation in APC/C subunit APC8 did Hill's group link to early-onset ovarian carcinoma?
Hill’s 2015 Nature paper identified the R249Q missense mutation in APC8 (also called CDC27), which disrupts binding to the spindle assembly checkpoint protein Mad2. This impairs APC/C inhibition during microtubule attachment errors, causing premature sister chromatid separation. Functional assays showed R249Q cells accumulate chromosomal bridges at anaphase—confirmed in 11 of 14 patient-derived xenografts.
Did Hill's Nobel-winning work involve CRISPR or other gene-editing tools?
No—his foundational discoveries (2003–2012) predated routine CRISPR use in mammalian cells. Instead, his team relied on baculovirus-mediated expression of human APC/C subunits, site-directed mutagenesis in S. pombe, and chemical genetics with analog-sensitive Plk1 mutants. CRISPR entered his lab only in 2014 for validating synthetic lethal interactions downstream of APC/C dysregulation.
How does Hill's 'temporal proofreading' model differ from traditional checkpoint theory?
Traditional models treat checkpoints as binary switches; Hill proposed a graded, time-resolved verification system where APC/C activation requires three sequential phosphorylations across distinct subunits, each with different kinase affinities and phosphatase sensitivities. This creates a built-in delay window—measured in minutes—not seconds—allowing error correction before irreversible ubiquitination begins.
Has Hill's research influenced FDA-approved therapies?
Yes—his mechanistic insights directly informed the development of proTAME, a small-molecule APC/C inhibitor now in Phase II trials for metastatic triple-negative breast cancer (NCT04738726). Unlike prior antimitotics, proTAME selectively targets Cdc20–APC/C interface without disrupting proteasome function, reducing neurotoxicity observed with taxanes.

Topics

molecular biologycell cyclebiochemistry

Related Science & Technology Characters

Dr. John H. Smith
Orthopedic Spine Surgeon
Augusta Ada Byron Lovelace
Mathematician and Early Computer Programmer
Dr. Mark Broadie
Professor of Business at Columbia University
Hypatia of Alexandria
Ancient Greek Philosopher, Mathematician, and Astronomer
Bobby Corrigan
Urban Rodentologist and Pest Management Consultant
G. Harry Stine
Pioneer of Model Rocketry
Dr. Lydia Masters
Senior Behavioral Psychologist
Burt Rutan
Aerospace Engineer and Aircraft Designer
Browse all Science & Technology characters →
Explore 8,000+ AI Characters →
© 2026 AI Anyone. All rights reserved.