Madeline Ho
Madeline Ho earned her B.A. in Chemistry from Carleton College and completed her Ph.D. at Northwestern University as a joint student in the Chen and Hoffman research groups under Profs. Lin Chen and Brian Hoffman. Her research focused on metalloenzymes, using advanced spectroscopic techniques—including EPR, ENDOR, and X-ray methods—to investigate their structure and function. Originally from San Diego, California, Ho graduated in June 2026 and will continue her research as a postdoctoral fellow in the lab of Prof. Ann McDermott at Columbia University.
What made you decide to attend Northwestern University?
I was drawn to Northwestern because I really wanted to do science in a rigorous but collaborative and friendly environment. The students I spoke to emphasized that despite Northwestern being a top-ranked chemistry department, there wasn’t a sense of competition amongst the graduate students, but rather that the department is a supportive and encouraging community. I have found this to be true in my own experience. Throughout my time here I have met a ton of really wonderful mentors, peers, and friends, who have devoted their time and effort to supporting me.
It also didn’t hurt that Northwestern is in such a great location! I have loved living in Chicago and getting to know the city.
How would you explain your research to someone outside of chemistry?
In the Hoffman lab we study metalloenzymes, which are enzymes that use metal centers such as iron or copper to catalyze interesting and difficult chemical reactions. Metalloenzymes are responsible for a ton of super important reactions in biology – for example, nitrogenase (Brian’s favorite enzyme!) uses a metal cofactor to convert nitrogen (N2) to ammonia (NH3), which plants can then use to make important molecules that are required for growth, like DNA and amino acids. Nitrogenase is responsible for producing something like ~1/3 of bioavailable nitrogen globally – meaning that this enzyme is responsible for a lot of the food we eat every day.
We use some pretty cool spectroscopic tools called Electron Paramagnetic Resonance (EPR) and Electron Nuclear Double Resonance (ENDOR; no relation to the planet from Star Wars!) to study these metalloenzymes. These techniques use microwave frequencies to probe unpaired electrons, and so they allow us to ‘zoom in’ on the metal cofactors of these enzymes and observe how their electronic structures change throughout a reaction.
Tell us more about the research you are conducting in Professor Brian Hoffman’s lab. What questions are you working to answer?
My projects have specifically focused on trying to characterize the electronic structures of iron-sulfur clusters, particularly cubane [4Fe-4S] clusters. Iron-sulfur clusters are one of the most ubiquitous metallocofactors in biology and play diverse roles, from simple electron transfers to participating in complicated multielectron redox chemistry. While ‘canonical’ [4Fe-4S] clusters are coordinated by four cysteine residues, there are many examples of ‘site-differentiated’ clusters in which one ‘unique’ iron is coordinated by a non-cysteine ligand. One of the main focuses of my PhD has been looking in-depth at some of these site-differentiated clusters and using EPR and ENDOR spectroscopy to probe how the identity of the unique ligand ‘tunes’ the electronic structure of the cluster, which can then ultimately impact its reactivity and biological function.
I have also done some cool work identifying new photochemistry in some of these site-differentiated clusters. We can use a laser diode to optically excite these clusters in the EPR cavity at cryogenic temperatures and monitor the subsequent photochemical reaction with EPR.
What has it been like to conduct research in a lab led by a faculty member who has helped shape Northwestern Chemistry over many decades?
It’s been awesome. The level of expertise available in the Hoffman lab is unparalleled and has been an incredible resource to tap into as a graduate student. It’s a unique experience to talk to people who not only know the foundational literature in my field, but who helped write it, and know many of the ‘key players’ personally. It’s been really cool to learn from Brian and others in the lab not just about science but also about the history of the field, and to hear their personal accounts of how certain ideas and discoveries developed over time.
Is there something Professor Hoffman has said, done, or modeled that changed the way you think about research?
Brian has modeled the value of collaboration in scientific research. Our lab works closely with a ton of other groups, both close to home at Northwestern and across the country and world. I admire that Brian is always willing and excited to form new collaborations when the scientific questions are interesting, even with early-career researchers who may be less established in the field. I also really admire how Brian has fostered so many long-standing collaborative relationships, some of which go back decades! I think these long-term collaborations really illustrate the strong sense of community that Brian cultivates, not just scientifically but also personally.
As a graduate student, collaborating with scientists who have different expertise and backgrounds than myself has helped me grow to see the ‘bigger picture’ of my research and understand where my skills fit within the broader field. I have been lucky to be able to work with a bunch of talented synthetic chemists, biochemists, and computational chemists.
Are there any moments, stories, or lab traditions from your time in the Hoffman Lab that have stayed with you?
One fun tradition in the lab is our annual March Madness pool, run by a Research Professor in the Hoffman Lab, Pete Doan! Every year an assortment of current and past Hoffman Lab members, as well as some assorted ‘friends of the lab’ join in to the pool. It has been really cool to be connected with people who were part of the lab before I joined. I don’t really follow college basketball, though, so the first year I participated in the pool, I filled out my bracket completely on ‘vibes.’ I did not even pay attention to the seed numbers, and did not realize that a lower seed number meant a better team. But after filling out my bracket almost completely randomly--I won!! It was definitely beginner’s luck, though, because every year since then I have done much worse. But I’m hoping to make a comeback next year!
As a student, what do you think your generation can learn from faculty like Professor Hoffman, whose careers have helped shape the department over many decades?
I think one message that young researchers can take away is that science should be fun! One of the most inspiring things about working for Brian is that 50+ years into his career, he’s still enjoying himself and doing work that he finds interesting. One of the first times I met Brian, he told me a story about how he was able to get a citation to a Sherlock Holmes story into a JACS paper – he always has some funny anecdote to share! I think the secret to having such a long and successful career is not only dedication and a commitment to scientific rigor but also maintaining a sense of curiosity and finding humor and genuine enjoyment in the work!