Dr. Anandi Krishnan, PhD Research Profile

  • MPNRF | January 27, 2025
    Profile:
    Dr. Anandi Krishnan, PhD
    Rutgers University

    Dr. Anandi Krishnan: A pioneer in collaborative MPN research 

    PhD
Stanford University

    Dr. Anandi Krishnan, PhD, believes that meaningful scientific breakthroughs don’t happen in isolation. In an academic world where scientific discovery often feels siloed, Dr. Anandi Krishnan’s new laboratory in the department of biomedical engineering at Rutgers University operates like a bustling intersection. She’s building an environment where researchers from sometimes disparate fields unite to decode the mysteries of myeloproliferative neoplasms (MPNs), a rare group of blood cancers. 

    The role of platelets in understanding MPN biology  

    At the heart of Dr. Krishnan’s work is the platelet — an essential component of wound healing and, as it turns out, a powerful tool for studying the dynamic ecosystem within our bone marrow — the bone marrow microenvironment (BME). “Platelet signatures can reflect the health and functional state of the bone marrow,” she explains. “They provide an excellent window for studying the bone marrow microenvironment without needing to do a bone marrow tap.” Scientists like Dr. Krishnan are hoping that the molecular insights into this otherwise hidden environment can be gleaned from sampling platelets circulating in the blood.

    One of the major activities of any cell is creating proteins. Protein synthesis starts with genes being read by cellular machinery and transcribed into messenger ribonucleic acids (mRNA or transcripts), which are in turn translated into proteins. By deciphering strands of RNA from within a cell, the scientists in laboratories such as Dr. Krishnan’s can determine what proteins are in the manufacturing pipeline. The process of studying the complete set of transcripts and gaining a holistic view of a cell’s activity is known as transcriptomics. 

    Transcription and Translation image Wikipedia For UTM

    Integrating –omic data to advance MPN research 

    To answer bigger questions, Dr. Krishnan engages with collaborators, integrating her data across scientific specialties such as proteomics (the study of proteins) and metabolomics (the study of metabolites). “I don’t want to think only about islands — ‘Oh, I work only on the transcriptome.’ I want my transcriptomic data to be incorporated with proteomic and metabolomic data so we can put the full picture together.” By matching complementary -omic data from timepoints along the protein production pipeline, Dr. Krishnan can make significant discoveries about the platelets of different groups of MPN patients. 

    Dry labs vs. wet labs: Bridging computational and experimental research 

    Dr. Krishnan’s focus on interdisciplinary collaboration is essential given her location at the intersection between multiple styles of laboratory work. “Our lab operates as both a dry lab and a wet lab,” she explained. “So computational and mechanistic research allows us to naturally bridge across disciplines.” While the ‘wet’ experiments occur at the laboratory bench and involve blood samples and transcript testing, the ‘dry’ experiments take place on computers, involving massive amounts of RNA data. A culture of open communication, mutual support, and interdisciplinary collaboration isn’t optional.

    “We take pride in sharing ideas and working together, which is crucial for scientific progress.” Dr. Krishnan referred to her laboratory’s supportive culture, stating, “We build community from here,” she states confidently. “They’re who become our family.” 

    Mentorship in science: Dr. Krishnan’s approach to building resilience 

    Dr. Krishnan’s collaborative ethos stems from her own experiences and extends to her mentorship style. As a woman, a mother, and someone from a nontraditional background, she’s acutely aware of the barriers that can prevent individuals from thriving in science. “I know how important it is to create a supportive environment rather than pushing people for a paper or data at the expense of human relationships,” she said. 

    Perhaps what makes Dr. Krishnan a superior mentor and principal investigator is her response to failure and the manner with which she teaches resilience. “Science and this career always involve constant obstacles and unexpected challenges,” Dr. Krishnan says knowingly. “I’ve learned to stay resilient in the face of challenges and approach problems with creative solutions.” 

    Her laboratory’s emphasis on personal respect and creativity bears fruit during the unpredictable process of scientific discovery. When she explained that “one should expect that hypotheses don’t always turn out as you want,” she’s highlighting a crucial lesson she imparts to students. Dr. Krishnan understands that the first thing a struggling student needs is to be heard. Once this supportive environment is established, setbacks are assessed, problem-solving begins, and resilience is taught. 

    Rebuilding with connections 

    Students from a variety of scientific specialties populate Dr. Krishnan’s new laboratory, but it was only recently that she re-entered her scientific career during a pandemic. Dr. Krishnan admitted how isolated she felt. “But perhaps necessity is the mother of invention,” she reflected, turning the conversation on a dime from a difficult memory to the solution that saved her. 

    She actively sought out collaborators both domestically and internationally, rebuilding her research network and accelerating scientific discovery. For example, a quick Zoom call inspired Dr. Krishnan to share her Cell Reports Medicine data with Dr. Ann Mullally, allowing the information to benefit Dr. Mulally’s ongoing research in a mouse model of MPNs. Her commitment to global teamwork resulted in the integration of her “plateletomics” data into the work of multiple other investigators. 

    Different pieces of the puzzle 

    Dr. Krishnan’s group is telling a new story about essential thrombocythemia (ET) and polycythemia vera (PV) MPNs from the perspective of the platelet. Leveraging her unique skills, her most recent discovery was made while comparing pre-protein transcript data to the protein data in a cohort of overseas MPN patients.   

    In a recent letter to the editor published in Blood Advances, Dr. Krishnan presented findings that validated her earlier research. The initial transcriptomic data revealed an overrepresentation of genes involved in “the unfolded protein response” at the mRNA level. The proteomic analysis in the recent letter confirmed that these same genes also showed increased expression of their proteins in MPN samples. This confirms the intricate connection between gene activity and protein outcomes. It also pinpoints a specific issue relevant to the platelets of patients with MPNs. 

    The specific group of genes over-represented in mRNA and protein levels in ET and PV samples are part of the “unfolded protein response.” Stressed cells switch on the transcription of this group of genes to restore balance and maintain normal cellular operations, a state known as homeostasis. This response is particularly relevant to MPNs because it sheds light on how cellular stressors — such as excessive protein production, oxidative stress, and inflammation, all of which are common in cancerous environments — may drive disease progression. These findings offer a deeper understanding of the molecular mechanisms driving MPNs and underscore the importance of integrating transcriptomic and proteomic analyses to uncover new therapeutic opportunities. 

    The power of community and team science in advancing MPN research 

    Whether coordinating efforts between basic and clinical scientists or building partnerships with international researchers, Dr. Krishnan’s focus remains on fostering a sense of shared purpose. “You do need to make that active effort to bring folks together,” she noted on the role of modern scientists. 

    Her leadership exemplifies how meaningful breakthroughs stem from the collective actions of a committed community. Her recent paper concludes by summarizing this ethos: “We demonstrate the immense value of cross-institutional collaborations in advancing larger-scale translational studies, particularly for rare disease cohorts” (Kelliher et al., 2024). 

    Dr. Krishnan’s work underscores that advancing MPN research requires more than scientific ingenuity; it demands an unwavering commitment to collaboration. By uniting people and ideas, she is setting a new standard for how science can be done. 

    To learn more about Dr. Krishnan and her career path, see this profile in which Dr. Krishnan discusses her return to academia: Discovering Science Yet Driven by the Heart | National Center for Advancing Translational Sciences.

    Sources:  

    Kelliher, S., Gamba, S., Weiss, L., Shen, Z., Marchetti, M., Schieppati, F., Scaife, C., Madden, S., Bennett, K., Fortune, A., Maung, S., Fay, M., Ní Áinle, F., Maguire, P., Falanga, A., Kevane, B., & Krishnan, A. (2024). Platelet proteomic profiling reveals potential mediators of immunothrombosis and proteostasis in myeloproliferative neoplasms. Blood Advances, 8(16), 4276–4280. https://doi.org/10.1182/bloodadvances.2023012016 

    Krishnan, A., & Thomas, S. (2022). Toward platelet transcriptomics in cancer diagnosis, prognosis and therapy. British Journal of Cancer, 126(3), 316–322. https://doi.org/10.1038/s41416-021-01627-z 

    Shen, Z., Du, W., Perkins, C., Fechter, L., Natu, V., Maecker, H., Rowley, J., Gotlib, J., Zehnder, J., & Krishnan, A. (2021). Platelet transcriptome identifies progressive markers and potential therapeutic targets in chronic myeloproliferative neoplasms. Cell Reports. Medicine, 2(10), 100425. https://doi.org/10.1016/j.xcrm.2021.100425 

    Tillmann, S., Olschok, K., Schröder, S. K., Bütow, M., Baumeister, J., Kalmer, M., Preußger, V., Weinbergerova, B., Kricheldorf, K., Mayer, J., Kubesova, B., Racil, Z., Wessiepe, M., Eschweiler, J., Isfort, S., Brümmendorf, T. H., Becker, W., Schemionek, M., Weiskirchen, R., … Chatain, N. (2021). The Unfolded Protein Response Is a Major Driver of LCN2 Expression in BCR–ABL- and JAK2V617F-Positive MPN. Cancers, 13(16), Article 16. https://doi.org/10.3390/cancers13164210 

     Tsai, Y. C., & Weissman, A. M. (2010). The Unfolded Protein Response, Degradation from the Endoplasmic Reticulum, and Cancer. Genes & Cancer, 1(7), 764–778. https://doi.org/10.1177/1947601910383011