The primary focus of our lab is to understand how changes in gene expression regulates cell fate transitions and function. Dysregulation of these processes, especially long-lasting epigenetic changes, are critical to many diseases. In particular, our laboratory focuses on how non-coding DNA elements act as “molecular switches” to causes changes in gene expression. We use different models to understand how non-coding DNA elements regulate which genes are on or off to regulate both normal cell functions but also disease. Currently my lab focuses on two models to address mechanistic questions.

1. Acute Myeloid Leukemia (AML). We focus on AML because it has a poor long-term survival even with high dose chemotherapy, illustrating the need for more effective, less toxic therapies. In AML, approximately 15% of patients have mutations within genes encoding the cohesin complex, which plays a critical role in allowing non-coding DNA elements to regulate gene expression. Most of our studies rely upon next-generation sequencing-based genome wide approaches, in addition to genomic editing to understand how cohesin mutations promote AML, with the goal being to develop more effective, less toxic therapies.
2. Hypertension.In many ways, hypertension represents one of the most widely studied human traits, because it is a critical mediator of cardiovascular disease. Genome wide association studies (GWAS) have identified thousands of single nucleotide polymorphisms (SNPs) which are associated with hypertension. Importantly, the overwhelming majority (>90%) do not reside within the coding region of genes. Our lab focuses on understanding whether these SNPs within noncoding regions of the genome can operate as molecular switches to alter gene expression and tries to define the mechanisms they use to regulate blood pressure. Our long-term goal is to translate this information into precision medicine approaches to best treat patients with hypertension.

   
   

• MCW Cancer Center IDEA award
  MPI- Drobyski (MCW) and Rao (Versiti
  01/2025-12/2025
  Immunologic and Molecular Determinants of Myeloid Sarcoma
• R01 AI183571
  MPI- Malarkanan (MCW), Rao (Versiti), Kee (University of Chicago)
  12/2024-11/2029
  GATA2-TGF beta-TAL1 pathway as a critical mediator of NK Cell development
• P01 HL149620
  Liang (PI), Role: Project 2, Project 3 and Core B Co-Investigator
  08/15/20-07/31/25
  Genetic and Epigenetic Mechanisms of BP Regulation
• R01 DK134064
  MPI-Battle and Rao
  08/01/22-05/31/26
  Defining GATA4’s Molecular Function in Gastric Cell Biology

Click Here for a full list of publications from Dr. Sridhar Rao

Selected Publications

• Kleman A, Singavi A, Pommert L, Mathison AJ, Hari P, Dhakal B, Mohan M, Janz S, Knight JM, Shah MV, Schinke C, Burns R, Steinhardt GF, Rao S, Carlson K. A timeline of genetic variant enrichment: from multiple myeloma diagnosis to myeloma-associated myeloid malignancy. Blood Adv. 2023 Sep 26;7(18):5549-5553. doi: 10.1182/bloodadvances.2022008953. PubMed PMID: 36724511; PubMed Central PMCID: PMC10514068.
• Liu Y, Huang J, Pandey R, Liu P, Therani B, Qiu Q, Rao S, Geurts AM, Cowley AW Jr, Greene AS, Liang M. Robustness of single-cell RNA-seq for identifying differentially expressed genes. BMC Genomics. 2023 Jul 3;24(1):371. doi: 10.1186/s12864-023-09487-y. PubMed PMID: 37394518; PubMed Central PMCID: PMC10316566.
• Coelho DR, Palma FR, Paviani V, LaFond KM, Huang Y, Wang D, Wray B, Rao S, Yue F, Bonini MG, Gantner BN. SOCS1 regulates a subset of NFκB-target genes through direct chromatin binding and defines macrophage functional phenotypes. iScience. 2023 Apr 21;26(4):106442. doi: 10.1016/j.isci.2023.106442. eCollection 2023 Apr 21. PubMed PMID: 37020964; PubMed Central PMCID: PMC10068561.
• Rao S. The kids are alright: MDS clones mature. Blood. 2023 Mar 16;141(11):1243-1245. doi: 10.1182/blood.2022019187. PubMed PMID: 36929441; PubMed Central PMCID: PMC10163310.
• Zorn KE, Cunningham AM, Meyer AE, Carlson KS, Rao S. Pediatric Myeloid Sarcoma, More than Just a Chloroma: A Review of Clinical Presentations, Significance, and Biology. Cancers (Basel). 2023 Feb 24;15(5). doi: 10.3390/cancers15051443. Review. PubMed PMID: 36900239; PubMed Central PMCID: PMC10000481.
• Rao S, Broglie L. HSCT for adults with immunodeficiencies. Blood. 2022 Oct 6;140(14):1580-1581. doi: 10.1182/blood.2022016422. PubMed PMID: 36201332; PubMed Central PMCID: PMC9707395.
• Pommert L, Schafer ES, Malvar J, Gossai N, Florendo E, Pulakanti K, Heimbruch K, Stelloh , Chi YY, Sposto R, Rao S*, Huynh VT, Brown P, Chang BH, Colace SI, Hermiston ML, Heym K, Hutchinson RJ, Kaplan JA, Mody R, O'Brien TA, Place AE, Shaw PH, Ziegler DS, Wayne A, Bhojwani D, Burke MJ. Decitabine and vorinostat with FLAG chemotherapy in pediatric relapsed/refractory AML: Report fromthe therapeutic advances in childhood leukemia and lymphoma (TACL) consortium. Am J Hematology,2022. 97(5); 613-622. PMCID: PMC8986610. *I was the biology chair for this study. My lab banked all samples and performed the detailed molecular studies published within this manuscript.
• Meyer AE, Stelloh C, Pulakanti K, Burns R, Fisher JB, Heimbruch KE, Tarima S, Furumo Q, Brennan J, Zhang Y, Viny AD, Vassiliou GC, Rao S. Combinatorial genetics reveals the Dock1-Rac2 axis as a potential target for the treatment of NPM1:Cohesin mutated AML. Leukemia. 2022. 36(8):2032-2041 PMCID: PMC9357218.
• Liang M, Cowley AW Jr, Greene AS, Geurts AM, Liu P, Liu Y, Rao S. Advancing Physiology with Expanded Multi-Omics. Function (Oxf). 2022;3(4):zqac031. doi: 10.1093/function/zqac031. eCollection 2022. PubMed PMID: 35801086; PubMed Central PMCID: PMC9247404.
• Pommert L, Schafer ES, Malvar J, Gossai N, Florendo E, Pulakanti K, Heimbruch K, Stelloh C, Chi YY, Sposto R, Rao S, Huynh VT, Brown P, Chang BH, Colace SI, Hermiston ML, Heym K, Hutchinson RJ, Kaplan JA, Mody R, O'Brien TA, Place AE, Shaw PH, Ziegler DS, Wayne A, Bhojwani D, Burke MJ. Decitabine and vorinostat with FLAG chemotherapy in pediatric relapsed/refractory AML: Report from the therapeutic advances in childhood leukemia and lymphoma (TACL) consortium. Am J Hematol. 2022 May;97(5):613-622. doi: 10.1002/ajh.26510. Epub 2022 Mar 8. PubMed PMID: 35180323; PubMed Central PMCID: PMC8986610.