Eric Alani

My research efforts are focused on understanding highly conserved mismatch repair (MMR) systems, which recognize and repair base pair and small insertion/deletion mismatches that arise as the result of DNA replication errors, DNA damage, and genetic recombination.  In humans, mutations in MMR genes correlate with a predisposition to a hereditary form of colorectal cancer (~2 to 7% of all colon cancers) and infertility, underscoring the importance of obtaining new mechanistic understandings of mismatch repair and diagnosis tools. My laboratory is funded the National Institute of Health and involves long-term collaborations with single molecule biophysicists and population geneticists.  The results of our efforts are a novel set of interdisciplinary approaches to study the roles of MMR in maintaining genome stability in yeast during vegetative growth and in meiosis. Our current work is focused on understanding how mismatch recognition proteins identify mismatches and recombination intermediates and signal downstream repair factors. 1. We are identifying novel roles for MLH1-MLH3 in forming crossovers that are critical for proper chromosome segregation in meiosis. Using genetic and biochemical assays we are studying how the complex acts alone or in concert with other proteins on a variety of DNA substrates, including those predicted to be recombination intermediates (e.g. branched structures, Holliday junctions). 2. We are analyzing the interaction of single MSH and MLH complexes with DNA using total internal fluorescence microscopy.  These studies will distinguish between competing models for how MSH and MLH proteins signal downstream steps in MMR. 3. We are using genetic and biochemical approaches to test how MMR components and newly identified factors prevent recombination between divergent DNA sequences, with the goal of understanding how such regulation impacts genome stability and cancer susceptibility. 

I care deeply about contributing to the scientific community. As part of this effort, I served on the editorial board of GENETICS, participated as an ad hoc member on many study section meetings, and co-organized several genome stability meetings.  In my department I served in many administrative roles including Director of Graduate Studies, NIH T32 Program Director, Department Chair, and Department Associate Chair. 23 Ph.D. students and eight post-doctoral fellows and 28 undergraduate students completed training in my group.  As an NIH Training Grant Director in Genetics and Development (2010-2014) I helped start a graduate student mentoring committee and a summer REU (Research Experience for Undergraduates) program emphasizing the recruitment of underrepresented minority (URM) students. 

I am committed to training and mentoring students to complete their Ph.D. degrees in a timely fashion and early-stage investigators.  I am also committed to promoting a safe and supportive research environment for students of all backgrounds, which includes supporting and advising them in their career decisions, providing them with ethically sound and responsible research practices, and ensuring their physical well-being.  Importantly, my group provides training in rigorous and unbiased experimental design.  

Selected Publications

• Bui DT, Dine E, Anderson JB, Aquadro CF, and Alani E.  2015.  A genetic incompatibility accelerates adaptation in yeast.  PLoS Genetics 11: e1005407.
• Manhart CM, Ni X, White MA, Ortega J, Surtees JA, and Alani E. 2017. The mismatch repair and meiotic recombination endonuclease Mlh1-Mlh3 is activated by polymer formation and can cleave DNA substrates in trans.  PLoS Biology 15: e2001164.
• Al-Sweel, N., Raghavan, V., Dutta, A., Ajith, V. P., DiVietro, L., Khondakar, N., Manhart, C. M., Surtees, J. A., Nishant, K. T., Alani, E. 2017.  mlh3 mutations in baker’s yeast alter meiotic recombination outcomes by increasing noncrossover events genome-wide.  PLoS Genetics 13:e1006974.
• Furman, C.M., Wang, T.-Y., Zhao, Q., Yugandhar, K., Yu, H., Alani, E.  Handcuffing intrinsically disordered regions in Mlh1-Pms1 disrupts mismatch repair. 2021. Nucleic Acids Res. 49:9327-9341.

2009, Carpenter Memorial Advising Award, Cornell University

My major teaching responsibility is BioMG6330, DNA Biology. This course covers the molecular biology and biochemistry of DNA metabolism.  Topics include DNA replication, genetic recombination, DNA repair, DNA damage checkpoints, DNA transposition, somatic hypermutation, and DNA editing technologies. Students will become familiar with these topics by reading papers in a journal club format that include genetic, biochemical, structural, and computational biology methodologies.

My overall goal is to prepare students to independently evaluate biochemical and genetic studies, to develop theories that support existing data, and to propose experimental approaches to test specific hypotheses. Students attend three hours of lecture per week, read original research papers that they then present and critically evaluate in a journal club, and write a series of reports based on an analysis of original research articles. A wonderful aspect of this course is that it describes rapidly evolving fields; this allows me to introduce new material and reorganize my lectures on a yearly basis. All course material (lectures, readings, problem sets, written assignments) is available through Cornell Canvas. 


My other teaching commitments include participating, organizing, or co-organizing Graduate Topics/Problems in Genetics and Biochemistry (BioMG7800), and lecturing in BioMG8369/BioMG7810, Foundations and Frontiers in Cellular and Molecular Biology. These courses are directed towards graduate students in the Fields of BMCB and GGD. I teach regularly in BioBM1320, Orientation Lectures in Molecular Biology and Genetics, mentor undergraduates in research (BioG4990), and serve as an Adhoc thesis reviewer in the Biology Honor Program.