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Biology was one among my favorite courses after I was in highschool, so I selected organic sciences as my main throughout my undergraduate research. However, earlier than my PhD coaching I by no means thought my profession would take me in the direction of being a PI. I undertook my PhD research on the University of Science and Technology of China (USTC), the place I labored on cell apoptosis and most cancers biology beneath the supervision of Mian Wu. The coaching expertise throughout my PhD research drove my private determination to additional my research as a postdoctoral researcher. I preferred the uncertainty of scientific analysis and the journey of going from an preliminary fascinating phenomenon to revealing the processes behind it. In 2008, I joined Xiaolu Yang’s lab on the University of Pennsylvania as a postdoc, the place I continued my research of p53 in tumours. Xiaolu supplied steerage and gave me the liberty and help to discover what I used to be serious about, which allowed me to develop my very own analysis route. During my postdoctoral coaching, I targeted on how metabolic adjustments in NADPH manufacturing underlie p53-medicated tumour suppression and located that p53 unexpectedly regulates NADPH metabolism by way of the pentose phosphate pathway and malic enzyme pathway, both transcriptionally or post-translationally. One of the research was printed in Nature in 2013. It was essentially the most thrilling factor I had skilled since I started analysis. At that second, I spotted my ardour for analysis and needed to proceed working in the direction of a tutorial profession as an impartial investigator.
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Credit: Wenjing Du
In 2016, I used to be again in China and began my very own lab on the Institute of Basic Medical Sciences (IBMS), Chinese Academy of Medical Sciences (CAMS) and School of Basic Medicine Peking Union Medical College (PUMC). Starting my very own lab as a PI was troublesome, and working a brand new lab in China is totally different from working one within the US, particularly when it comes to ready for funding and gear from abroad. In the primary 12 months I encountered sudden challenges, similar to beginning a lab with just one small room that also needed to be furnished and geared up, recruiting individuals and securing funding. Eventually, with the assistance from mates and colleagues, I overcame the difficulties and was lucky sufficient to recruit gifted individuals who needed to work with me.
When all the pieces settled down, we started to do experiments in early 2017. The analysis within the lab centred on just a few matters, similar to how most cancers cells rewire their metabolism, the function of tumour suppressors and oncogenes of their metabolic regulation, and the way nutrient alteration is sensed by most cancers cells. Based on my earlier research and others’ findings, NADPH shortage is believed to be a limiting step in cell proliferation. I’ve at all times been curious concerning the physiological function of NADPH in cells past its function in antioxidant defence and lots of biosynthetic reactions. To this finish, we began to review how cells sense mobile NADPH change. Manipulating mobile NADPH ranges was the essential step for this challenge. We knocked down or overexpressed the NADPH-producing enzymes (malic enzymes, glucose-6-phosphate dehydrogenase or mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase) to scale back or improve mobile NADPH ranges. However, as enhancing metabolic enzymes might be affecting middleman metabolism past NADPH, we wanted to discover a option to immediately manipulate NADPH focus in cells. We couldn’t add NADPH to cell tradition medium as a result of NADPH is unable to cross the cell membrane. We puzzled whether or not NADPH might be transfected into cells like DNA. We examined this chance from a wide range of angles and eventually discovered one reagent that might certainly transfect NADPH into cells. We tried it on a number of cell strains and examined the mobile NADPH concentrations after transfection, and it labored! In 2021, the primary main paper that got here out of my lab, on how NADPH was sensed and the perform of NADPH in modulating mobile epigenetic standing (Li et al., https://doi.org/10.1038/s42255-020-00330-2), was printed in Nature Metabolism. The paper describes a metabolism-independent perform of NADPH in modulating epigenetic standing and transcription. Mechanistically, NADPH immediately interacts with histone deacetylase 3 (HDAC3) and interrupts the affiliation between HDAC3 and its co-activator nuclear receptor corepressor 2 (Ncor2; SMRT) or Ncor1. By interrupting the advanced between HDAC3 and Ncor, NADPH suppresses HDAC3 exercise and reprograms histone acetylation and gene expression. Although how NADPH acts on HDAC3 wants additional clarification, NADPH might have broad impacts on cell physiology by way of modulation of epigenetic standing and transcription.
The problem for us throughout this challenge was that the COVID-19 pandemic compelled us to shut the lab for round two months throughout manuscript revision. Then, with a gradual reopening, just one or two individuals have been allowed to work within the lab concurrently. During that point, we fearful concerning the sluggish progress. We have been lucky to satisfy considerate editors who supported us and gave us enough time, so we might absolutely deal with the reviewers’ feedback. And we have been additionally fortunate to have the help of my collaborators, who helped us carry out docking and molecular dynamics simulation experiments between NADPH and HDAC3 through the revision of the paper. Moreover, we felt fortunate and inspired to have assist from the editorial group {and professional} reviewers. The feedback from reviewers have been constructive, and the editor summarized the factors that have been notably essential, which was particularly useful in exhibiting a younger lab tips on how to revise a paper. I’m additionally lucky to have passionate trainees who work arduous and commit their careers to analysis.
The paper in Nature Metabolism gave my lab a very good begin and was additionally significant for my skilled life as a junior PI. It introduced many constructive issues for my group and for myself and opened a brand new route and collaboration for my analysis group. After the paper was printed, it drew some consideration to my work and my lab, together with awards and invites to talk at conferences, and I hope that it will present itself extra sooner or later, when it comes to recruiting individuals and securing funding.
Being a PI is just not simple. Having my very own lab is thrilling however difficult, as I have to fulfil my duties for my trainees, my collaborators and my division. As a brand new PI, I encountered many challenges that I had not anticipated, though these are in all probability widespread to most new PIs. Finding the correct postdocs and college students was harder than I anticipated; for instance, after I recruited the primary scientist for my lab, the candidate cancelled the appointment someday earlier than the interview. Fortunately, I managed to recruit gifted and passionate workers scientists and college students who needed to affix my lab and work with me. My lab slowly grew from a small lab with just one workers scientist and one scholar in 2017 to a much bigger lab with two workers scientists and 6 college students right this moment. I believe recruiting individuals is an important factor for a brand new PI and I’d counsel being affected person till you discover the correct individuals to your lab.
As a lady, I’ve at all times been requested how I steadiness my private life and my skilled obligations. I’ve to say that it’s arduous to obviously separate private {and professional} lives. As a PI, it appears that you’ve got tons of labor to do on a regular basis, similar to writing funding proposals, writing manuscripts, instructing, supervising trainees, and attending seminars and conferences. Balancing the workload was particularly difficult through the COVID-19 pandemic in 2020, when faculties have been closed. My two youngsters needed to keep house and take their courses on-line. During the daytime, I needed to take care of them and tackle the function of an elementary faculty trainer, and solely after they went to mattress at night time might I begin my very own work. It was a tough time and I’m happy with all the pieces that I’ve overcome. I’m lucky to have a really supportive household, which incorporates my particularly supportive husband, Peng Jiang, who can be my scientific collaborator. Therefore, I by no means attempt to separate my private {and professional} life; I at all times take my job with me wherever I am going. I believe retaining these elements of your life separate doesn’t matter if your loved ones is supportive. However, I nonetheless suppose some work–life steadiness is important. The optimum work–life steadiness will fluctuate over time as a result of all of us have totally different priorities and obligations and there’s no good mannequin that matches everybody. The steadiness is correct so long as you obtain a way of accomplishment and pleasure out of your work or your life, and personally, I hope that I’ll progress far in my profession and on the identical time take pleasure in life with my household.
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