A couple of weeks ago I learned that one of my science heroes, Dr. Namandje Bumpus, was promoted to full Professor at Johns Hopkins School of Medicine – and named Director of the Department of Pharmacology and Molecular Sciences! This makes her the first Black woman to become a department director at Hopkins Medicine and – currently – the ONLY Black woman chairing a pharmacology department at any medical school – in the entire United States. I think it’s important to recognize the rarity of these appointments, because it’s strong evidence of the systemic racial inequalities inherit in science, medicine, and academia. And it sure makes for some eye-catching headlines, but please don’t stop at the headlines. Dr. Bumpus EARNED that spot. She has done years of really cool, and potentially life-saving, work on how the body processes drugs used to treat HIV and other diseases, and I want to tell you some more about her *and* her work.
I don’t remember how I first learned about Namandje Bumpus, but I definitely remember when I first met her! It was a couple of weeks after I had written a profile of her as part of a “WiSE Wednesday” series featuring female scientists for CSHL WiSE, and I saw that she was presenting an award lecture at a conference I was at – so I went to go see her – and I even introduced myself and got a picture with her. I shared my contact info with her and she actually emailed me back – and has emailed me several times since to check in and offer support. Pretty much as soon as a saw her talk I realized she needed a Wikipedia article written about her, so I made one. And it was such a pleasure to get to update it with her new appointments. (I know the directorship probably sounds more impressive than the professorship, and the directorship is a HUGE honor – but becoming a tenured full Professor is also a HUGE accomplishment – one that’s really really rare for Black people, especially Black women, and one that ensures some career stability).
Writing her Wikipedia article, I learned a lot about her, so I will tell you more about that at the end, but first I want to tell you more about her work, because it gets less attention than it deserves and don’t want it to get drowned out by all the headlines of “Firsts.” Speaking of which, I strongly encourage journalists and scicommers to please, every time you write one of the “became the First (second, etc.) —— to ——— “ think to yourself, “would I be writing this sentence if the person were a White male?” If no, why is that? Recognize the systemic inequalities that led to it. And then go a step further – think to yourself, “what would I be writing about this person if they were a White male?” – their WORK! So write about that work too!
I’m so tired of hearing all this excusivising for panels and committees and speakers sessions featuring mostly all White males by saying “there weren’t qualified females, there weren’t qualified minorities” YES THERE ARE! (you make it super hard for them to succeed, but they do succeed). I’m so tired of hearing people say that when minorities get appointed to positions it’s just *because* they’re minority – that they “had it easy” – are you kidding me?! So here – today I give you proof that Black women are doing incredible scientific work, despite the injustices in our system. That they deserve to be here. That many many more of them deserve to be here. And that the excuses need to stop.
note: I wrote this part about her work last April. So she’s likely done even more incredible science science then, but this is the work I got to hear about in her talk.
Namandje Bumpus studies anti-HIV drug metabolism – metabowhatta? Metabolism is just a term we use to describe the chemical changes our body makes to molecules, and metabolite’s what we call the changed version. When you ingest a chemical that’s in one form, that’s not necessarily the form it stays in as it travels throughout your body and “does its thing.” You take some drug, your liver does something to it and, bam – it’s a metabolite.
Just like the food you eat gets processed, the pharmaceutical drugs you take do too. They’re already pretty small (much smaller than that bite of sandwich) but they can still get broken down further. And they don’t just get broken down, they can also get added onto or just tweaked a bit. All of these changes fall under “metabolism” and it’s a big focus for pharmacologists, because these changes can affect the drugs’ activity – either positively or negatively.
A lot of this metabolism occurs in your liver, and it’s “evolutionarily-designed function” is to detoxify (make unharmful) harmful things you might accidentally eat. So it’s sometimes nicknamed your body’s “detox center.” When you ingest something, your body wants to “screen” it, so it gets sent to the liver after being absorbed into the bloodstream in your intestines. The blood cycles through about once per minute. So even though the liver can’t modify it all the first time, it gets more and more chances.
A lot of the metabolism that occurs is done by a family of protein enzymes (reaction mediators) called Cytochrome P450s (CYPs). CYPs are responsible for metabolizing ~75% of drugs on the market, but this work is split up among 57 family members. These guys are “heme-containing monooxygenases” -> like hemoglobin, they use heme as a cofactor to hold onto an iron atom. This iron atom then helps transfer oxygens onto things one (mono) at a time, “oxidizing them”
This is a so-called phase 1 metabolic reaction – it paves the way for phase 2 (conjugation) in which another protein adds a bigger, more water-loving (hydrophilic) group to it (often a gluturonic acid) that makes it more soluble so it can get excreted more easily (you can pee them out instead of having them stored in your fat). pharmacology isn’t my field, but this video explains it really well: https://www.youtube.com/watch?v=uOcpsXMJcJk
You definitely don’t want them building up, but too much peeing it out (drug clearance) and there’s not enough active drug to act. So dosages have to be carefully calculated and monitored.
And one aspect of Bumpus’ work looks at this connection. She worked out the pathway of metabolism of several anti-HIV drugs (Riplivirine (RPV) is in the pic). She found that genetic variants in CYPs can make them more or less active at metabolizing some of these drugs. So some patients might have drugs buildup while others need higher doses. This sort of thing is the realm of “pharmacogenetics” – the idea is that, for drugs where there is a known difference based on what version of a specific gene you have (the genotype) doctors should take that into account when prescribing a dosage – or maybe they need to prescribe a different drug altogether.
Sometimes, the liver “gets it wrong” and makes non-harmful or at least not-very-harmful things more harmful -> TOXIC METABOLITES. These can wreck havoc, especially in the liver. Such toxic metabolites can be a cause of drug-induced liver failure in patients taking antiviral drugs to treat HIV and hepatitis C (HPC).
Bumpus researches what metabolites form when patients take them, how they form, where they go, how they cause problems, how we can tell they’re causing problems before things get too bad, and whether we can keep them from causing problems. That’s a lot of work – and she’s amazing! It’s was such an honor to meet her at #EB2019 last year! And now we’re in email contact! And she remembered me!
Anyways – she had to develop new ways to detect and accurately measure the metabolites using a technique called mass spectrometry (mass spec), which splits molecules up into charged fragments (ions) and measures their masses, then matches the masses up to what you’d expect from different metabolites.
The hope is that, by figuring out how toxic metabolites form, they can design drugs that are still active but don’t form toxic metabolites. And by figuring out why they’re toxic they might be able to do something to block the off-target effects of the metabolites without blocking the on-target effects.
So that’s a case in which metabolism removes drugs, but sometimes metabolism “makes” drugs – some drugs are actually given as “prodrugs” – they’re not functional until enzymes in your cells take a whack at them. And this is the case with another type of anti-HIV drug Bumpus studies, tenofivir. It works by tricking a viral molecule into thinking its a DNA letter (nucleotide) and trying to stick it into a growing DNA chain then getting stuck so they can’t copy themselves. More about how they work here: http://bit.ly/2D2AynW
But tenofivir only has one phosphate, and DNA letters have to have 3 to be added. So they don’t work until they’ve been phosphorylated twice so that they look like DNA. Bumpus is working out which kinases (phosphate-adders) do the phosphorylating. And she’s finding that the kinases are different in different types of cells, which can have implications that need to be taken into account if the drugs are given in different routes (like oral vs. topical). She’s also finding that some patients have variants in the kinases that might make them less responsive to the drug, which could explain part of the reason that some patients contract HIV even though they take the drug prophylactically (to prevent infection).
Working on her Wikipedia article, I came across this great quote of hers: “don’t be daunted by your own or others’ perceptions of what a scientist looks like or what his or her background should be. Just go after it, if it’s what you want to do.” http://bit.ly/2IkHPDX
You can watch her describe her work in her own words: https://youtu.be/bzbUukfhlW4
Some more about her…
In addition to carrying out this critical research, before her recent promotion, Bumpus served as Associate Dean for Basic Research at the John Hopkins University School of Medicine. In this position she helped facilitate the combination of “basic research” which seeks to answer fundamental scientific questions and “translational research” that seeks to put those findings to use, for example in a clinical setting.
She also serves as a science commissioner and member of Washington, D.C.’s Science Advisory Board, chairs the NIH’s Xenobiotic and Nutrient Disposition and Action study section, serves on the PhRMA Foundation’s Basic Pharmacology Advisory Committee, and edits the journal Drug Metabolism and Disposition. And last year she was elected Councilor of ASPET (the American Society for Pharmacology and Experimental Therapeutics).
Bumpus earned a bachelor’s degree in biology from Los Angeles’ Occidental College, followed by a Ph.D. in pharmacology from the University of Michigan-Ann Arbor. She then did a postdoctoral fellowship at the Scripps Research Institute. Her many honors include one from a president himself – President Obama awarded her a Presidential Early Career Award for Scientists and Engineers. She also received 2014 Tanabe Young Investigator Award from the American College of Clinical Pharmacology and ASPET’s 2015 Drug Metabolism Early Career Achievement Award.
Bumpus is one of far too few Black female professors in the biomedical field and she’s working to change this. She served as Hopkins’ first associate dean of institutional and student equity and instituted mentoring programs to expand access to resources and opportunities. We thank Bumpus for her work and congratulate her on her recent promotions!
if you want to learn more about how you can help improve the diversity of Wikipedia articles, here are slides I made from when I hosted a @CSHL_WiSE/@CSHLibrary #WomenInSTEM Wikipedia edit-a-thon (shoutout to Dr. Jess Wade for the inspiration!):
I also did a post on Wiki editing that might help: http://bit.ly/wikieditingguide
#365DaysOfScience All (with topics listed) 👉 http://bit.ly/2OllAB0