BBA Rising Stars 2024: Winners announced

We offer our warmest congratulations to the winners of the 2024 BBA Rising Stars Special Issue and Prize.

This biennial initiative aims to recognize the accomplishments and promise of scholars in the early stages of their independent careers and draw international attention to their research.

BBA Rising Stars Special Issue

The BBA Rising Stars Special Issue draws together papers published across most BBA journals in one issue. All papers are from researchers within 10 years of completing their PhD (career breaks are taken into account) and have been identified by the Executive Editors of the BBA family journals as having the potential to influence future research directions in biochemistry and biophysics.

2024 BBA Rising Stars Prize winners

What do you think has been your most influential work to date, and why?

My most influential work to date is the study titled "Simvastatin increases temozolomide‐induced cell death by targeting the fusion of autophagosomes and lysosomes." Conducted as my postdoctoral project with Dr. Ghavami and Dr. Klonisch at the University of Manitoba, Canada, this research highlighted the pleiotropic effects of statins, distinct from their cholesterol-lowering properties, by uncovering their impact on cellular trafficking and autophagy flux. We demonstrated that simvastatin selectively disrupts the autophagic process by inhibiting the fusion of autophagosomes and lysosomes, a mechanism that sensitizes glioblastoma cells to temozolomide-induced apoptosis. This finding not only advances our understanding of statins’ diverse biological roles but also opens new avenues for repurposing established drugs in cancer therapy. By leveraging autophagy modulation, this study contributes to innovative combination therapies and provides a promising strategy for enhancing chemotherapeutic efficacy and overcoming resistance in aggressive tumors.

What do you see as the future direction of research in your field?

I see the future direction of research in cell biology heading toward a comprehensive, integrative understanding of cellular signaling pathways and their interactions. Instead of isolating and analyzing individual components, future research will emphasize examining the dynamic interplay between these pathways, observing cellular functions as interconnected processes. This holistic approach will allow us to appreciate how various signaling cascades converge to determine cell fate and behavior.

To illustrate this, I often refer to the story of the “elephant in the dark.” In this tale, individuals touch different parts of an elephant, each forming a limited perception based on their partial view. Similarly, current cell biology research often focuses on isolated pathways, resulting in fragmented insights. The future lies in illuminating the “whole elephant,” where we move beyond studying one part at a time and begin to see the full picture—understanding how these pathways interact, affect each other, and collectively determine cell outcomes. This approach will unlock a deeper comprehension of cellular behavior and open doors for innovative therapeutic strategies that consider the cell’s entire network of interactions.

What is one piece of advice you would want to give to other researchers in the early stages of their careers?

One piece of advice I would give researchers in the early stages of their careers is to find your true passion and focus your work in that area. Pursue what genuinely matters to you and what you deeply care about. Research is full of challenges, and the dedication it requires can only be sustained if you are driven by a sincere interest and a strong sense of purpose. When your work aligns with your passion, it not only fuels your motivation but also enhances your resilience in the face of setbacks and obstacles. Following your true interests will make your journey in research fulfilling and impactful.

What do you think has been your most influential work to date, and why?

Much of my research has focused on mitochondrial calcium signaling, leading to several influential discoveries in the field. Two of my works stand out as particularly influential. The first involves uncovering the unconventional role of mitochondrial calcium uptake 1 (MICU1), a known regulator of the mitochondrial calcium uniporter (MCU). This work was conducted during my postdoctoral training in John Elrod’s lab at Temple University. Our research revealed MICU1's role in cristae remodeling and mitochondrial architecture, showing its interaction with MIC60, a component of the mitochondrial contact site and cristae organizing system, independent of its traditional role as a gatekeeper of mitochondrial calcium uptake. This work establishes MICU1 as a calcium sensor that affects mitochondrial structure and function through previously unknown mechanisms, influencing cellular energetics and survival. The second major contribution is the identification of the MCU as a sensor for reactive oxygen species, conducted during my postdoc in Muniswamy Madesh’s lab at Temple University. Our findings demonstrated that the Cys-97 residue in MCU undergoes modifications such as S-glutathionylation, leading to higher-order oligomerization. This results in increased calcium uptake and mitochondrial reactive oxygen species production, enhancing cell death under calcium overload conditions. This discovery underscores the unique role of Cys-97 in cellular stress responses, marking a significant advancement in understanding MCU’s regulatory functions.

What do you see as the future direction of research in your field?

The future direction of research in mitochondrial calcium signaling lies in decoding the complex regulatory mechanisms of mitochondrial calcium sensing and its integration with broader mitochondrial pathways to maintain cellular health. Emerging evidence suggests that mitochondria are very heterogeneous in terms of ultrastructure, organization, and function. One rule does not apply to all; for example, an increase in the oxygen consumption rate is not always beneficial, a smaller number of cristae per mitochondrion is not always detrimental and increased mitochondrial calcium uptake does not necessarily lead to more beneficial outcomes. A broader perspective will help us better understand the complexity of mitochondria, paving the way for managing diseases associated with mitochondrial dysfunction. Our research group is focused on uncovering the molecular roles of MICU proteins and other mitochondrial calcium sensors beyond their conventional and known functions, a largely unexplored area. We aim to identify novel MICU targets and examine their impact on mitochondrial calcium flux, mitochondrial architecture, and cell-specific roles in mitochondrial regulation. This work will provide deeper insights into how mitochondrial calcium signaling shapes bioenergetics, ionic balance, and structural integrity, potentially leading to novel therapeutic avenues for addressing human diseases associated with mitochondrial dysfunction.

What is one piece of advice you would want to give to other researchers in the early stages of their careers?

My advice to early-stage researchers is to remain open to learning from peers, mentors, and your own experiences. Identify your strengths, leverage them, and be proactive in expanding your thinking, scientific reasoning, and skill set. The journey to becoming a skilled researcher and educator is continuous, and adopting a mindset that embraces growth and adaptability can make a lasting impact. Celebrate and recognize every step forward, no matter how small. The path of research is often challenging, filled with setbacks and rejections. If a grant or paper isn’t accepted on the first attempt, don’t be disheartened; revision and resubmission are key components of long-term success. Stay persistent, keep applying, adapt to feedback, and continually refine your approach. Building resilience and maintaining passion will drive both your personal growth and contributions to the field.

Chris performed a brief postdoc at ASU’s Biodesign Center where he performed X-ray Free Electron Laser crystallography and cryo-EM. Chris then performed a postdoc at Yale University’s Department of Chemistry where he studied aspects of photosynthesis including photoacclimation, metallocofactor assembly, and water oxidation.

Chris opened his lab at the University of Wisconsin-Madison Department of Biochemistry in fall 2024. His group investigates the molecular bases of photosynthetic protein complexes. Chris is an NIH Pathway to Independence Award awardee, an ARCS Scholar, and specializes in the molecular mechanisms of photosynthesis.

What do you think has been your most influential work to date, and why?

I think my most influential work so far has been determining the crystal structure of the Type I reaction center complex from Heliobacteria. Photosynthesis researchers had understood the photooxidoreductases involved in oxygenic photosynthesis (photosystems I and II) and a subset of those involved in anoxygenic photosynthesis for a long time, but the Type I reaction center structure was a missing link for understanding how photosynthetic reaction centers have evolved to diversity we see today. After determining that structure, many papers have been published revealing interesting similarities and differences among extant reaction centers, and we now have a clearer picture of how the first reaction center looked ~3 billion years ago.

What do you see as the future direction of research in your field?

Presently, my group how certain cyanobacteria acclimate to different light conditions, how the water-splitting cofactor of photosystem II is assembled, and radiation damage to metal cofactors in cryo-EM experiments. My group is likely to expand our studies into cryo-electron tomography and in situ single-particle studies. Furthermore, we hope to engineer characteristics into photosynthetic organisms, tailoring them for different environments.

What is one piece of advice you would want to give to other researchers in the early stages of their careers?

Don't be afraid to fail! We tend to advertise our successes and not our failures. For me, resilience in the face of failure has been a much more valuable trait than intelligence.

Martin earned two doctoral degrees from the University of Leipzig, in Biology (2014) and Molecular Oncology (2015), followed by a postdoctoral fellowship at the Dana-Farber Cancer Institute. His contributions to cancer research have been recognized with multiple awards, including two dissertation awards. Martin also serves as a peer reviewer for over 40 scientific journals and major funding bodies, sharing his expertise to support advancements in cancer biology and genomics.

What do you think has been your most influential work to date, and why?

I believe that my most influential work concerns the tumor suppressor p53 and the regulation of cell cycle genes. In 2014, we were one of several teams that uncovered that p53 does not directly repress target gene expression, challenging the longstanding belief that it could act as both a transactivator and a transrepressor. This finding was significant because it shifted the understanding of p53’s role in gene regulation within the context of cancer biology.

Instead of acting as a transrepressor, we demonstrated that p53 employs an alternative indirect pathway by utilizing its target p21 to reactivate the transrepressor complexes DREAM and RB:E2F. This mechanism enables p53 to effectively downregulate cell cycle genes, providing a nuanced understanding of how p53 regulates cellular proliferation in response to stress signals.

Building on these findings, we generated gene signatures that provide robust readouts for other researchers. These gene signatures serve as critical tools for studying regulatory networks of p53 and the cell cycle. They also help us to understand the broader implications of their activation in various cellular contexts, including cancer development and progression.

What do you see as the future direction of research in your field?

In the first decade of this century, many p53 research groups shifted their focus from studying gene and protein regulation to broader cancer biology. The advent of omics technologies has revived interest in p53-mediated gene regulation and attracted new research groups. More

recently, established genome research teams have begun to recognize p53 as a powerful tool for addressing questions related to genome regulation, leading to exciting new insights.

As we look to the future, p53 research is poised for significant advancement, particularly in understanding its interactions with chromatin in different genomic contexts. As we deepen our knowledge of p53’s multifaceted interactions with other transcription factors and chromatin regulators, long-held beliefs about its function will likely be re-evaluated and refined. This research avenue promises to unveil new insights into the molecular mechanisms governing p53’s actions. Ultimately, it will enhance our understanding of its contributions to cancer biology and pave the way for novel therapeutic strategies.

What is one piece of advice you would want to give to other researchers in the early stages of their careers?

I often recall the advice from my postdoctoral mentor, James DeCaprio: “What is the question you are asking” the importance of clarity and focus in your research. Clearly defining your research questions will guide your experiments and analyses.

Additionally, I encourage early-career researchers to maintain a critical mindset. The scientific field contains misconceptions and long-held beliefs that may not withstand scrutiny. Do not hesitate to challenge established ideas when new evidence contradicts them. Embracing curiosity and skepticism will enhance your research and promote a culture of critical thinking within the scientific community.

What do you think has been your most influential work to date, and why?

Although recent, I believe my most influential work has been on the global control of transcription at the single-cell level opens in new tab/window. In collaboration with colleagues in Zurich, we conducted a genome-wide screen with single-cell resolution to quantify global transcription rates as they relate to cell size and cell-cycle stage. We made so many interesting observations in this work that really changed how I think about transcriptional regulation. For example, we found that gene-specific and total mRNA concentrations are precisely maintained in mammalian cells, even in the context of major perturbations to cell size and RNA metabolism. Part of the mechanism responsible involves coordinating RNA Polymerase II abundance with cell size, and with global RNA decay rates. This work will be influential because it raises so many questions, including how the transcription machinery is globally adjusted but also shared in the correct amounts between the genes that need to be expressed? how does stochastic (bursty) transcription lead to stable mRNA concentrations? and also whether, and how, global RNA concentration is being sensed by cells to control other RNA metabolic rates?

What do you see as the future direction of research in your field?

There are currently two major approaches in the gene regulation field. The first, more traditional one, employs biochemistry, genetics, and genome sequencing—typically focusing on how different regions of the genome are regulated, or on the molecular mechanisms of transcription. The second makes use of recent imaging technologies, to observe cell-to-cell variability in chromatin states and transcription rates, and to track single molecules over time in living cells. The conceptual pictures that emerge from these two approaches are very different. For example, genomics typically focuses on very precise but static snapshots averaged over cell populations, and often conceptualizes results on a one-dimensional “average gene.” Imaging, on the other hand, emphasizes dynamics, spatial organization, and cell-to-cell variability. We have a long way to go, but I am excited about helping to bring these different “worlds” together to a more complete understanding of gene regulation in space and time.

Another important direction is towards multivariate readouts at the single-cell level. The more information we have about each cell, the more we see that they are all unique, with characteristics that depend on their current state, environment, and history. The expression of the genome is both cause and consequence of this cellular “phenotype.” We therefore need to better situate studies of gene regulation within the context of other cellular changes, such as changes in metabolism or spatial organization.

What is one piece of advice you would want to give to other researchers in the early stages of their careers?

Just like a single cell, you are unique! Cultivate your unique talents and characteristics, whether that’s in graphic design, writing, mathematics, computer programming, networking, or organization. Science thrives on diverse skills. You will find ways to use your strengths to collaborate effectively, and, if it’s what you love, then you’ll have fun doing it.

What do you think has been your most influential work to date, and why?

That’s a great question. I believe my most influential work was when I applied for the first time Raman spectroscopy to investigate adipose tissue from different locations (The Analyst, 2018, 143, 5999). In this study, I demonstrated that the lipid unsaturation degree, an important spectroscopic marker indicating chemical changes in lipid composition, varied significantly among different types of adipose tissues and was influenced by factors like age, location, and phenotype. This research was inspired by the lecture on the role of perivascular adipose tissue in obesity and vascular damage presented by Professor María Fernández-Alfonso from Universidad Complutense de Madrid, during her visit to JCET in 2018. This paper marked my initial contribution to this field opening a new chapter in my research by introducing spectroscopy to study lipid changes in adipose tissue in mouse models of atherosclerosis and obesity.

What do you see as the future direction of research in your field?

I would say that the future of research in my field lies in personalized medicine and targeted therapies which open up new possibilities for treating a wide range of diseases. This aligns closely with the mission of my Institute, where I work now, JCET JU, established and led by Professor Stefan Chłopicki, which is dedicated to the area of endothelial/vascular biomedicine. Recently, there has been a growing interest in perivascular adipose tissue as a key player in cardiovascular and metabolic diseases. Individual variations in its function, driven by genetic, environmental, and lifestyle factors, suggest that personalized treatments for metabolic disorders could be highly effective. For instance, a better understanding of how adipose tissue responds to diet, exercise, and pharmacological interventions could lead to more effective, customized strategies for managing obesity and metabolic diseases.

What is one piece of advice you would want to give to other researchers in the early stages of their careers?

The advice I would give to early career researchers is to be patient and not let failures discourage you. Success has many paths, so stay flexible, embrace change, and find the approach that works best for you. The people around you also play a crucial role. Seek out a research group aligned with your interests and an open-minded leader. A good mentor can guide you through key decisions, help you avoid pitfalls, and offer invaluable support. I was fortunate to work with Professor Agnieszka Kaczor, my PhD supervisor, to whom I owe much of my knowledge, experience, and scientific curiosity. Building a strong network early in your career is also essential. Cultivating connections with fellow scientists can lead to unforeseen collaborations and valuable opportunities. Attend conferences, engage with researchers whose work you admire, and do not hesitate to ask questions.

In 2018, he joined Professor Nigel Scrutton’s group at the Manchester Institute of Biotechnology, studying how protein dynamics influence electron transfer. Since 2020, he has been a University Assistant at the Graz University of Technology in the Institute of Molecular Biotechnology. As a BioTechMed-Graz-funded group leader, his research focuses on enzymes that play a vital role in host-pathogen interactions.

What do you think has been your most influential work to date, and why?

So far, I view my PhD work on fungal electron transfer reactions and their vital role on cellulose degradation as the defining work of my career. It not only laid the foundation for my postdoctoral research, but also contributed to subsequent research on enzymatic biomass conversion.

What do you see as the future direction of research in your field?

Being interested in enzyme mechanisms and engineering, the continued advancement of artificial intelligence will shape the future of biochemistry in terms of innovation and application.

What is one piece of advice you would want to give to other researchers in the early stages of their careers?

Identify an area of research that excites you and where your contributions can make a unique impact. It is also important to build a good relationship with mentors who can guide and support you in the beginning of your academic career.

What do you think has been your most influential work to date, and why?

I think the most influential work that I have been involved in began during my PhD, where I investigated the structure-function relationships of TNF receptors and uncovered new mechanisms to modulate TNF receptor 1 (TNFR1) signaling, which plays a key role in inflammatory and cell death pathways. We have demonstrated that disruption of receptor-receptor interactions by competitive inhibition (SLAS Discovery, 2017; ACS Bio and Med Chem Au, 2023) and perturbation of receptor conformational dynamics through allosteric modulation (Science Signaling, 2019; Protein Science, 2020) by small molecules are both feasible approaches to modulate TNFR1 signaling. We have also found that long-range structural couplings, between TNFR1 membrane distal and proximal domains, mediated through the ligand-binding domain, are potent actuators and can be controlled allosterically. In my own lab, we have further identified the inter-monomeric spacing between the pre-ligand TNFR1 dimer as a novel binding pocket and demonstrated that binding of an inhibitory peptide at this location could alter receptor conformational dynamics and disable receptor–ligand signaling complex (PNAS, 2024). In summary, we have shown that TNFR1 conformational states can act as a molecular switch in determining its function and are important therapeutic targets. By applying these molecular insights to translational high-throughput screening, we have discovered novel receptor-specific modulators, greatly advancing therapeutic targeting of TNFR1 signaling for treatment of autoimmune and inflammatory diseases. I am privileged to work with an exceptional team of passionate students and researchers in my group, all dedicated to advancing innovative approaches to targeting TNF receptor signaling. I am deeply grateful to my PhD advisor, Jonathan Sachs at the University of Minnesota, for introducing me to this field and for being an inspiring and supportive mentor and a role model throughout my PhD journey and beyond.

What do you see as the future direction of research in your field?

Future research in membrane protein studies and drug discovery is promising, with several key directions poised to drive significant advancements. High-resolution structural biology tools like cryo-EM and X-ray crystallography now reveal intricate protein structures, facilitating more precise drug design. Computational modeling and artificial intelligence (AI) are expediting drug discovery by predicting protein structures and ligand interactions, allowing for rapid optimization before experimental testing. Novel drug modalities, such as nanobodies, peptides, and proteolysis targeting chimeras (PROTACs), provide new avenues for targeting membrane proteins or native ligands with greater specificity. Meanwhile, recent studies, including ours, are focusing on allosteric modulation, which enable drugs to act on alternative binding sites and specific pathways, potentially reducing side effects. Finally, targeting entire membrane protein complexes instead of individual proteins opens the door to highly selective therapies. Together, these research directions hold immense potential for advancing our understanding of membrane proteins and translating this knowledge into innovative therapies, particularly for diseases that currently have limited treatment options. With continued interdisciplinary collaboration and technological advancements, membrane protein studies will likely remain at the forefront of drug discovery and biomedical research in the coming years.

What is one piece of advice you would want to give to other researchers in the early stages of their careers?

As an early-career investigator who recently transitioned to an independent research position, I have found that maintaining agility has been invaluable. This advice, passed on to me by my mentor, has proven crucial in navigating the complexities of academia. Staying agile means being adaptable to evolving research trends, open to interdisciplinary approaches, and resilient in the face of challenges. It involves continuously refining your research focus, embracing new methodologies, and being responsive to feedback from peers and mentors. In an academic environment where priorities can shift rapidly, the ability to pivot, reassess, and adjust your strategies can make a significant difference in achieving long-term success and impact.