Category Archives: Blog

Hey Isabel here, I’m a third year PhD student in the CAMB/DSRB graduate program. In the Anguera lab we are especially interested in dosage compensation, a mechanism to balance the gene expression of the X chromosome between females and males. But why and how is dosage compensation achieved?

Typically chromosomes are identical between females and males, except when it comes to the sex chromosomes. Differences in sex chromosome composition can result in an imbalance of gene expression. For example, in mammals the X chromosome has a larger contribution of gene expression than the Y. Therefore, females who have two Xs (XX) have an added challenge of regulating double the X-linked gene dosage compared to males who have one (XY). Fortunately, nature has come up with an elegant system to address this problem. All placental mammals (XX/XY) equalize gene expression through X-Chromosome Inactivation (XCI), an epigenetic process to transcriptionally silence one of the female X chromosomes. Proper dosage compensation is critical for female development and must be maintained in every somatic cell to prevent overexpression of X-linked genes commonly seen in autoimmune diseases such as Systemic Lupus Erythematosus. Between different placental mammalian species there are minor differences in how XCI is initiated and maintained, however all species rely on the long non-coding RNA XIST to achieve XCI. Surprisingly, the closely related marsupial (like the kangaroo) also inactivates a single female X chromosome, but does not rely on the long non-coding RNA XIST to achieve dosage compensation in this system.

Outside of mammals, other organisms also face the challenge of unequal gene expression from the sex chromosomes. In flies, such as the popular model organism Drosophila melanogaster, the sex chromosomes are similar to mammals in that females are XX and males are XY. However, flies achieve dosage compensation through a completely different mechanism. In this system it is the male fly which alters its gene expression, doubling the expression of their single X to equalize to the female XX expression. Another interesting example of the variety in dosage compensation mechanisms can be seen in the worm Caenorhabditis elegans. In these worms females are XX while males are XO. The female worms downregulate each of their X chromosomes by half to compensate for the single male X.

I find it amazing how dosage compensation mechanisms have evolved so differently to solve the same basic problem. This underscores the absolute importance of maintaining strict control over X-linked gene expression. As a graduate student in the Anguera lab, my goal for my thesis is to better understand how dosage compensation and XCI is maintained, and how disruption of this process could lead to female-biased disease susceptibility. I am very excited to delve deeper into studying the epigenetic mechanisms regulating XCI.

Hi there, I’m Camille. As a sixth year CAMB/DSRB graduate student who recently defended, I’m finishing up my time as a PhD student in the Anguera Lab. Research in the Anguera lab focuses on the epigenetic process of X-chromosome inactivation, which happens in women to equalize X-linked gene dosage between the sexes. We are very motivated to understand why women compared to men have a higher risk for developing autoimmune disorders like lupus, and we hypothesize that there is a genetic basis in the number of X chromosomes underlying this female bias. I’m interested in uncovering how unique mechanisms of X-chromosome inactivation in immune cells may be involved in female-biased autoimmunity.

Graduate students experience lots of ups and downs throughout the process of obtaining a Ph.D. Looking back on my time as a graduate student, I have definitely experienced those highs and lows. I found that one of the most challenging moments happened during the last few months before my thesis defense. In a short amount of time, I had to balance writing my dissertation, submitting and revising manuscripts, and traveling to postdoc interviews, all while trying to be a functional human being. In the end though, these tasks ended up going hand-in-hand, and I felt that the postdoc interviews were the best preparation for the day of my dissertation. I also owe a lot to my Anguera Lab mates for making me feel well prepared and for hosting a wonderful post-defense celebration!

I feel very fortunate to have been one of the founding members and first graduate student of the Anguera Lab. It has been a lovely experience to watch the lab grow over the years, both in size and in the development of new research avenues. Thanks to wonderful leadership and mentoring from Montserrat, the Anguera Lab continues to be a great place to be a trainee, and I’ve also learned a lot about what it’s like to be a junior investigator and to set up your own lab. I’m looking forward to cheering on my fellow Anguera lab graduate students as they develop their own really exciting research projects and move closer towards defending. After my time in the Anguera comes to an end in a few short weeks, I am excited to remain in the Epigenetics Institute as a Postdoctoral Fellow in the Blobel lab.

Briana Renn wasn’t sure what career path she wanted to follow, then she took a free 4-week program on reproductive sciences and her outlook changed. She had always been interested in the role genetics plays in our daily lives, so when her middle school teacher sent an e-mail out about the program, she decided to apply along with one of her friends. She initially didn’t get in – but her friend did, and hearing about what she was doing each session made her want to participate even more, so she reapplied and was selected for the next session.

The program – the Penn Academy for Reproductive Sciences (PARS) – is an all-female workshop led by expert clinicians and scientists, that incorporates a mix of small-group discussions, demonstrations, and hands-on lab activities to explore current research topics in reproductive health. Briana really enjoyed the hands-on aspect of the program, where she was able to work with mouse embryos and isolate her own DNA. She heard about real-life fertility scenarios when a physician from Penn gave a guest lecture, and learned about the roles genetics and epigenetics plays in our reproductive health. The experience sparked her interest in reproductive health and led her to apply for and successfully enroll in Temple’s nursing program.

Working in a lab setting and gaining real-world insight into the science behind fertility is not something you may experience in a typical high school class, so Briana enthusiastically advises anyone who is interested in a STEM career to apply for PARS, even if you’re not sure what career path you want to follow. You may just find your calling in life.

PARS is supported in part by grant P50 HD068157-06A1 from the National Institutes of Health. To learn more about the program, visit their website: https://irm.med.upenn.edu/science-impacting-the-clinic/education-outreach/pars/

Hi, I’m Mariel. I’m a third year graduate student joint between Ben Garcia and Shelley Berger. My research mainly focuses on the mechanisms of the metabolic enzyme ACSS2, which converts acetate to acetyl-CoA, which can then get incorporated into lipids and histone proteins. This enzyme is important because a lot of cancers overexpress ACSS2, so understanding its role will provide insight into how these cancer cells can adapt, especially in hypoxic areas within tumors.

Being a shared student between two epigenetics labs has been a great experience. I get to use mass spectrometry as a tool in understanding a lot of different epigenetic mechanisms that we are interested in figuring out in the Berger lab. After being in the lab for almost two years now, I’ve learned so many cool things about mass spec and how powerful it is in answering a lot of biological questions. Also, being in both labs has been very helpful for me because I get to be around a lot of awesome grad students and postdocs who are very knowledgeable in different areas of expertise. There is always someone to ask for help if I want to try CRISPR, purify proteins, or optimize mass spec methods for my project. It has been a really unique opportunity to be a part of both labs.

One of the great things about being in Ben’s lab is the very supportive environment. Everyone in the lab is very encouraging and friendly. Also, Ben has created a very unique lab environment where despite the large group, we still get to know our labmates and build friendships outside of work. He brings us to ASMS and HUPO conferences each year, hosts lab parties in his house, and takes us to lots of happy hours. During one of the lab parties, we did a murder mystery party where everyone dressed up as a hero or a villain, and Yekaterina was murdered by Laura who ended up taking over the whole planet!

Overall, as a grad student, I really enjoy being a part of Ben’s lab because of the very productive and supportive lab environment. Being a joint student makes it more exciting because I get to use mass spectrometry in answering a lot of different questions we have in epigenetics.

I’m Dylan, a 5^th year graduate student in Ben Garcia’s lab. My research focuses on the use of proteomics to study how the histone code can be dysregulated in cancer. By studying histone modification patterns in both normal and tumor tissue, we have been able to identify better diagnostic markers and suggest new therapeutic targets in diverse cancer types.

The best thing about being in Ben’s lab is being able to be a part of such a diverse and talented group. At the moment, there are close to 30 of us in the lab. We come from all over and we do lots of different things. Many of our experiments require the use of nanoLCs, analytical instruments that enable us to perform liquid chromatography at flow rates lower than 0.5 µl/min. About a year ago, we started getting confused because we had acquired so many of the same make and model, so someone proposed that we name them after countries that people in the lab come from. We now have instruments named: India, China, South Korea, Russia, Poland, Italy, Panama, Dominican Republic, and the Philippines. And that doesn’t even cover everybody in the lab. It is not uncommon at all to hear languages other than English spoken in the lab, and I truly appreciate that. Plus, the potluck dinners are awesome. Have you ever tried maduros with kheer? I cannot recommend it enough.

The range of skill sets in the lab is also really impressive. We have people with backgrounds in everything from Computer Science to Chemistry and Physics to Immunology. On any given day, someone is coding, someone is differentiating stem cells, someone is purifying protein, and someone else is developing a crazy new mass spectrometry method. Whatever experiment I can dream of, there will be someone in the lab who has the right expertise for me to brainstorm with or consult with every step of the way. Ben is always around to provide feedback and guidance, but he allows us to devise our own way to approach problems. On top of this, we have ongoing collaborations with groups all around the world working on a staggering variety of biological questions. In a single lab meeting we will go from hearing about a nanofluidic device that allows for sampling the proteome of a single cell to hearing about the effect of the gut microbiome on histone modifications in the intestinal epithelium, and no one bats an eye. It’s a lot of fun.

I feel that Ben has really put together something special here: he is committed to promoting diversity in science in every sense of the word, and he is as supportive as can be. It’s a privilege to be a part of this team.

I am Ramya Billur, a post-doctoral fellow in the Black lab at UPenn’s Department of Biochemistry and Biophysics. I am presently investigating PARP-1 functions in DNA repair and transcriptional regulation.

Since my childhood, I would often think about how a few milligrams of drugs could effectively treat a disease. This inspired me to take up Chemistry and Genetics in my undergraduate and graduate studies. During the course of my undergraduate studies, I learned the basic concepts of Genetics and Chemistry. I always felt that there was some clue missing in the replication mechanism of the HIV virus that contributed to why it is a pandemic disease, coupled with the lack of available anti-HIV drugs, made me realize that I should focus my studies in science to help reveal the many biological mysteries out there. My fervor towards Chemistry was unappeasable and impelled me to pursue a Masters degree in Industrial Chemistry at Jawaharlal Nehru Technological University Hyderabad (JNTUH) in India. I was actively involved in the synthesis of substituted aryl dithiocarbamic acid methyl esters, novel Aurora-A kinase inhibitors, and chalcones mediated by TFAA-H₃PO₄.

Further, I pursued my PhD in Chemistry at the University of Louisville under the mentorship of Dr. Muriel Maurer. My dissertation mainly focused on employing NMR, ITC, and HPLC techniques to characterize how the blood coagulation enzyme thrombin, and its precursor prothrombin, utilize ligand binding exosites to control its functions. My involvement in collaborations, as well as my attendance at various conferences and workshops, and a dire need to develop drugs for cancer treatment inspired me to specialize my career in cancer research.

Due to the strong medical significance of PARP-1 in cancer biology, and the Black lab being a leading expert in applying hydrogen deuterium exchange mass-spec (HXMS) to characterize protein structure and dynamics, I began my postdoctoral training in this lab to understand PARP-1 dynamics. The Black lab has been very helpful in teaching me various biophysical techniques. I am excited to decipher various biological mysteries and specialize my career in structural biology using a biophysics platform to impact biomedicine.

Hi, I’m Alice, a rotation student in Ben Black’s lab. I’m currently working with Praveen on the stoichiometry of centromere assembly and centromere-kinetochore interaction during mitosis.

I am a first-year graduate student from the Chemistry department, the only one with a Chemistry background in this lab. I began my scientific research in a group focused on biomimic, biological nanopore sequencing. Single molecule detection, visual nanopores on a platform, next generation sequencing, everything was so fascinating to me as an undergraduate student and I really enjoyed investigating the unknown with curiosity and efforts. This exciting endeavor, although sometimes painful when facing the possibility of endless failure, drove me to pursue a PhD.

I decided to continue studying Chemistry, but became more and more interested in Biology, especially DNA and protein structure and their function in living organisms. Luckily, I found the crossroad of these two subjects, and decided to move forward in studying epigenetics. I’ve finished two rotations since last semester, the first on nucleosome structure with X-ray crystallography, followed by DNA modification quantification by mass spectroscopy. The great power of analytical techniques and their broad applications made me want to learn Cryo-EM, which led me to Ben Black’s lab.

Ben is a warm-hearted and thoughtful person. When I first saw him, I was surprised that he wrote everything in a notebook and talked about my rotation project in a very clear manner. My interests lie in the research of the core centromeric nucleosome complex and its transformation during mitosis, so he prepared a project combining my formal research experience and my interests in his lab. He considers so much for a rotation student like me, which makes me really motivated.

The environment in Ben’s lab is quiet but friendly. Every time I encounter a hurdle in an experiment, my colleagues are willing to help with patience. They are enthusiastic about their own research, I feel like I could see stars shining in their eyes when they are talking about their projects! Their passion inspires me and drives me to further learn about CENP-A biology. Also, I’ve had the chance to collaborate with other labs, and participate in weekly Chromo Club meetings to learn more about this field. I quite enjoy my life here and hope I will get the chance to be a member of this lab.

I’m Praveen, a post-doctoral fellow in the Black lab at the University of Pennsylvania. My current research focuses on understanding centromere-kinetochore functions during cell division.

My background is in biochemistry and my first experience related to research in life sciences was while undertaking my masters in biochemistry, studying life from the molecular perspective. I was really intrigued by how every molecule has its own role to play in biology in an orchestrated fashion. My interest in research simply arose from curiosity and having spent a lot of time looking at animations describing various biological processes.

My research training started with grad school, where I looked into various aspects related to mitochondrial biology and their role in protein import. After graduation, while looking to broaden my research area, I found myself fascinated by chromosome biology and the contributions of the Black lab in answering the most pressing questions in this field. At the same time, advances in Cryo-EM technology shifted my focus to CENP-A biology. This generated great enthusiasm, and I am excited to learn new things and understand the molecular details of the most stable DNA-protein complex at the centromere.

The Black lab is a strong structural biology research group with a broad range of interests related to chromosome biology. The lab provides the opportunity to work with novel biochemical and biophysical techniques and provides opportunities to learn new skills. The Black lab actively contributes to the scientific community through its scientific interactions and multi-lab group meetings across several departments, programs, and schools at UPenn.

The Black lab is my first international working experience and I find it very refreshing to work with friendly and cooperative people. We constantly help each other in improving our scientific skills and moving forward constructively. We also like to pique the interest of undergraduates who may be interested in discovering the secrets of biology. Our group effort in happy hours and yearly retreats helps take the edge off from the stress of research and refreshes us so we can tackle problems in research.