Jonathan (Jon) Stefely

The Stefely Lab

Education

B.S., 2009, University of Notre Dame, Chemistry (Marvin J. Miller)

Ph.D., 2015, University of Wisconsin-Madison, Biochemistry (David J. Pagliarini)

M.D., 2019, University of Wisconsin-Madison

Residency, Clinical Pathology (2019-2023), Massachusetts General Hospital

Fellowship, Transfusion Medicine (2021-2022), Brigham and Women’s Hospital

Postdoctoral, 2023-2026, Massachusetts General Hospital and Broad Institute (Vamsi K. Mootha)

Honors & Awards

2008 McKnight Prize in Undergraduate Chemistry, Second Place

2012 NIH Ruth L. Kirschstein National Research Service Award (F30) (2012–2015)

2019 Pathology Honor Society

2019 Alpha Omega Alpha Medical Honor Society

2021 Vickery-Colvin MGH Pathology Research Award

2023 Scott Murphy Award, Biomedical Excellence for Safer Transfusion (BEST) Collaborative

2025 NIH Mentored Clinical Scientist Research Career Development Award (K08, NIAID) (2025–present)

Research Interests

Our laboratory focuses on comparative metabolism from pathogenic amoeba to humans.

The high-level question driving our work is: how does our human metabolism differ from that of distant eukaryotic relatives such as pathogenic amoeba?

Our core scientific thesis is that a systematic characterization of the unique metabolism of pathogenic amoeba that is not conserved in humans will lead to the discovery of both new fundamental biology and novel drug targets.

Amoeba are ancient single-cell eukaryotic organisms found across the globe in diverse environmental niches. Amoeba can be considered evolutionary cousins to humans, sharing some biochemical pathways, but diverging in many interesting ways – which we aim to systematically delineate. Some amoeba are human pathogens that can cause infectious blindness or fatal brain infections. Unfortunately, diagnosing amoeba infections is challenging, and current treatment options are often ineffective. The divergent biochemical features of amoeba can offer opportunities for creative new diagnostic or therapeutic targets. However, most of this unique amoeba biochemistry remains uncharacterized.

To systematically discover unique features of amoeba biology and biochemistry – with a particular focus on metabolism – our scientific approach integrates large-scale multi-omics, high-throughput microscopy, and computation with mechanistic biochemistry, organelle physiology, and cell biology.

Importantly, the amoeba we study are also part of a larger group of infectious eukaryotes called protozoans, which collectively impact approximately one billion people per year. Protozoan pathogens found locally in Wisconsin include infectious amoeba, tick-borne Babesia (co-incident with lyme disease), and water-borne Giardia. Globally, the most infamous protozoan pathogen is Plasmodium, which causes malaria and affects ~300 million people each year. Across many protozoan pathogens, new drug targets and diagnostic strategies are in demand. While we focus on amoeba, we hope that our fundamental science will have a broader impact on this widespread group of protozoan pathogens that have a devastating global impact.

Publications

• Mitochondrial protein functions elucidated by multi-omic mass spectrometry profiling (PMID: 27669165)
• Biochemistry of Mitochondrial Coenzyme Q Biosynthesis (PMID: 28927698)
• Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase Activity (PMID: 27499294)
• Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis (PMID: 25498144)