Degrees

Ph.D., chemistry and chemical biology, Northeastern University (2018)
B.S., chemistry, biochemistry concentration, Warren Wilson College (2012)

Professional Training and Experience

Postdoctoral fellow, Vanderbilt University (2023–2024)

Howard Hughes Medical Institute postdoctoral fellow, University of California, Berkeley (2018–2023)

Visiting scientist, National Cancer Institute (2015) 

NSF-REU researcher, Wellesley College (2011)

Research Interests

Professor Marcus's research has focused (and will focus in the future) on how proteins evolve new biological roles—particularly ATPase and GTPase hydrolytic enzymes. Both classes of proteins likely share a common ancestor but have adapted to distinct functions within cell biology. ATPases more often perform mechanical work, while GTPases frequently act as signaling switches, despite both functioning through nucleotide hydrolysis.  Differences in biological outcomes can originate from the unique biochemical and structural characteristics encoded within a protein's sequence. For example, changes to a sequence can modify how a protein moves, or how a protein interacts with other biological partners to propagate biological events.  How these characteristics change over time is reflected in the relationships of protein sequences within an evolutionary track. 

The paths through which ATPase and GTPase enzymes functionality diverged from one another remain unclear, and many aspects of their biophysical and signaling landscapes are still not well-studied. These proteins are also implicated in a range of diseases, such as cancer, where mutations often lead to new or dysregulated biological pathways. Understanding both the commonalities and specificities within different branches of protein evolution can shed light on how these diseases persist.

This work takes a deeply holistic approach to questions of protein diversification, utilizing computational methods such as bioinformatics, AI-based protein modeling, and molecular dynamics simulations, to interrogate the theoretical physics and evolutionary paths of related proteins. Observations from these computational experiments inform the design and execution of high-throughput biophysical assays to test how these principles hold up in vitro. Finally, her lab will solve new protein structures using tools such as X-ray crystallography and cryo-EM to "see" how evolution changes protein structure. 

Teaching Interests

Courses taught by Professor Marcus explore how the biological universe employs chemical and physical principles to develop and sustain life. With a diverse teaching background spanning from general chemistry to molecular biophysics and protein chemistry, she integrates cutting-edge literature to elucidate foundational scientific concepts. This approach not only enhances comprehension of recent breakthroughs but also fosters anticipation of future discoveries. Additionally, Professor Marcus emphasizes collaboration in scientific inquiry through group-based projects and activities, highlighting the cooperative nature of scientific advancement. She is also interested in investigating broader topics such as scientific communication, the intersection of academic and industrial research, and systemic inequalities, all of which shape our scientific understanding and collective direction.

Selected Publications

For full bibliography, see Professor Marcus's Google Scholar: https://scholar.google.com/citations?user=QQfEZcIAAAAJ&hl=en

ORCID ID: 0000-0002-2869–6703

Marcus K, Huang Y, Subramanian S, Gee C, Gorday K, Ghaffari-Kashani S, Luo XR, Zheng L, O'Donnell M, Subramanian Sr, Kuriyan J Autoinhibition of a clamp-loader ATPase revealed by deep mutagenesis and cryo-EM. Nat Struc Mol Bio. 31(3), 424–435. PMID: 38177685 (2024)

Yang K, Wang C, Kreutzberger A, Ojha R, Kuivanen S, Couoh-Cardel S, Muratcioglu S, Eisen T, White IK, Held RG, Subramanian S, Marcus K, Pfuetzner RA, Esquivies L, Doyle C, Kuriyan J, Vapalahti O, Balistreri G, Kirchhausen T, Brunger AT. Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein. Proc Natl Acad Sci USA. 119. PMID: 35982670 (2022)

Marcus K, Mattos C. Water in Ras superfamily evolution. J. Comput. Chem. 41(5), 402–414. PMID: 31483874 (2020)

Marcus K, Mattos C. Direct attack on RAS: intramolecular communication and mutation-specific effects. Clin. Cancer Res. 21(8) 1810-1818. PMCID: 2587836 (2015)