PIPages
Labs

Michael James Emanuele

University of North Carolina at Chapel Hill, NC·Biochemistry

Every time a cell divides, the amounts of hundreds of its proteins rise and fall on a strict schedule. Much of that timing comes from controlled protein destruction, and when the controls fail, cells can divide when they should not or damage their DNA — problems linked to cancer and neurological disease.

Fields

Biochemistry

Biology

Genetics

Topics

cell cycle

ubiquitin

protein degradation

Grants
1 known grant, through Mar 2029

What they work on

  1. Define the wave of protein destruction occurring in G2 and at the G2-to-mitosis transition, determining which proteins are degraded and when, and how the phosphate-adding enzyme PLK1 controls this program, using proteomics and cell-based assays.
  2. Identify the E3 ubiquitin ligases — the enzymes that select proteins for tagging and disposal — responsible for G2 degradation, and test how their activity shapes a cell's decision to continue dividing after stress or damage.
  3. Characterize deubiquitinases (enzymes that remove ubiquitin tags) flagged by computational and proteomic screens as having unstudied cell cycle roles, measuring their kinetics and substrate preferences and identifying their targets.
  4. Determine structures of these deubiquitinases bound to the E3 ligases they antagonize using cryo-electron microscopy, to explain mechanistically how tag addition and removal are balanced during division.

More about the research

This research asks which enzymes decide when particular proteins are destroyed during the division cycle, and what that timing accomplishes.

Why it matters

Faulty control of protein disposal underlies human diseases including cancer and some neurological disorders. By naming the enzymes that set protein levels across the division cycle, the proteins they act on, and the structures through which they work, this research could reveal regulatory steps that go wrong in proliferating cells and point toward enzymes worth targeting with drugs.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Proteostasis signaling in cell cycle control

NIH · Apr 2024 – Mar 2029

Closest labs

Stephanie Gates

University of Missouri-Columbia, MO·Biochemistry

Dissect how the Hsp70/CHIP/BAG-1 chaperone complex affects each step of proteasomal degradation, including ubiquitin tagging, substrate binding and breakdown, using in vitro assays with purified proteins.

Angela Mabb

Georgia State University, GA·Neuroscience

Determine whether tagging of the deubiquitinase OTUD4 with ubiquitin by the enzyme RNF216 makes OTUD4 less stable, and whether the OTUD4 mutation found in Gordon Holmes syndrome makes the protein more stable.

David Morgan

University of California-San Francisco, CA·Biochemistry

Determine how cyclin-dependent kinases (Cdks), enzymes that tag proteins with phosphates, build complex multisite phosphorylation patterns on their substrates in the eukaryotic cell cycle, using biochemical approaches.

The school

University of North Carolina at Chapel Hill: 72 labs on PI Pages, $1.6B a year on research, 523 research doctorates a year.

More about University of North Carolina at Chapel Hill

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