Craig brooks
Faculty Member
Last active: 3/14/2019

Profile

Acute kidney injury (AKI) occurs in ~13% of hospitalized patients and is associated with a fourfold increase in mortality. AKI also predisposes patients to chronic kidney disease. AKI also predisposes patients to chronic kidney disease (CKD), which affects ~10% of the world's population. Renal proximal tubule epithelial cells (PTCs) are vital to the function of the kidney and are also integral to the pathology of the injured kidney, as the most sensitive kidney cell type to ischemia and nephrotoxic insults. The overall goal of my research is to delineate the molecular mechanisms of PTC cell injury/death, survival and subsequent regeneration to identify therapeutic targets to treat AKI. To this end, I investigated mechanisms of PTC cell death. I was the first to demonstrate pathological mitochondrial fragmentation in PTCs during kidney injury, leading to cell death, (Brooks et al. JCI 2009) and demonstrate the therapeutic potential of inhibiting mitochondrial fragmentation using small molecule inhibitors. I also demonstrated a direct interaction between Bcl-2 family proteins and mitochondrial morphology proteins (Brooks et al., PNAS, 2007; Brooks et al., AJP Cell 2011). Next, I focused on the role of PTCs in regulating inflammatory processes during AKI. I found tubular cell phagocytosis suppressed inflammation (Yang, Brooks et al., J. Clinical Inv., 2015) as well as induced autophagy, which in turn, inhibited proximal tubular cell activation of T cells through MHC presentation (Brooks et al., EMBO, 2015). Current research interests include: Further delineating the mechanism and therapeutic potential of autophagy activation in the regulation of immune processes in AKI; Determining if the activation of novel cell cycle regulators following AKI contributes to fibrosis and chronic kidney disease through induction of mTOR-LC3 associated pro-secretory phenotype; and examining if mitochondrial dynamics proteins, such as mitofusins, modulate autophagic flux in AKI.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Cyclin G1 and TASCC regulate kidney epithelial cell G-M arrest and fibrotic maladaptive repair. Canaud G, Brooks CR, Kishi S, Taguchi K, Nishimura K, Magassa S, Scott A, Hsiao LL, Ichimura T, Terzi F, Yang L, Bonventre JV (2019) Sci Transl Med 11(476)
    › Primary publication · 30674655 (PubMed) · PMC6527117 (PubMed Central)
  2. RAGE-aptamer attenuates deoxycorticosterone acetate/salt-induced renal injury in mice. Taguchi K, Yamagishi SI, Yokoro M, Ito S, Kodama G, Kaida Y, Nakayama Y, Ando R, Yamada-Obara N, Asanuma K, Matsui T, Higashimoto Y, Brooks CR, Ueda S, Okuda S, Fukami K (2018) Sci Rep 8(1): 2686
    › Primary publication · 29422652 (PubMed) · PMC5805738 (PubMed Central)
  3. Gene-Edited Human Kidney Organoids Reveal Mechanisms of Disease in Podocyte Development. Kim YK, Refaeli I, Brooks CR, Jing P, Gulieva RE, Hughes MR, Cruz NM, Liu Y, Churchill AJ, Wang Y, Fu H, Pippin JW, Lin LY, Shankland SJ, Vogl AW, McNagny KM, Freedman BS (2017) Stem Cells 35(12): 2366-2378
    › Primary publication · 28905451 (PubMed) · PMC5742857 (PubMed Central)
  4. KIM-1/TIM-1 in proximal tubular cell immune response. Brooks CR, Bonventre JV (2015) Oncotarget 6(42): 44059-60
    › Primary publication · 26683362 (PubMed) · PMC4792540 (PubMed Central)
  5. Meclizine Preconditioning Protects the Kidney Against Ischemia-Reperfusion Injury. Kishi S, Campanholle G, Gohil VM, Perocchi F, Brooks CR, Morizane R, Sabbisetti V, Ichimura T, Mootha VK, Bonventre JV (2015) EBioMedicine 2(9): 1090-101
    › Primary publication · 26501107 (PubMed) · PMC4588407 (PubMed Central)
  6. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Freedman BS, Brooks CR, Lam AQ, Fu H, Morizane R, Agrawal V, Saad AF, Li MK, Hughes MR, Werff RV, Peters DT, Lu J, Baccei A, Siedlecki AM, Valerius MT, Musunuru K, McNagny KM, Steinman TI, Zhou J, Lerou PH, Bonventre JV (2015) Nat Commun : 8715
    › Primary publication · 26493500 (PubMed) · PMC4620584 (PubMed Central)
  7. KIM-1-/TIM-1-mediated phagocytosis links ATG5-/ULK1-dependent clearance of apoptotic cells to antigen presentation. Brooks CR, Yeung MY, Brooks YS, Chen H, Ichimura T, Henderson JM, Bonventre JV (2015) EMBO J 34(19): 2441-64
    › Primary publication · 26282792 (PubMed) · PMC4601664 (PubMed Central)
  8. KIM-1-mediated phagocytosis reduces acute injury to the kidney. Yang L, Brooks CR, Xiao S, Sabbisetti V, Yeung MY, Hsiao LL, Ichimura T, Kuchroo V, Bonventre JV (2015) J Clin Invest 125(4): 1620-36
    › Primary publication · 25751064 (PubMed) · PMC4396492 (PubMed Central)
  9. TIM-1 signaling is required for maintenance and induction of regulatory B cells. Yeung MY, Ding Q, Brooks CR, Xiao S, Workman CJ, Vignali DA, Ueno T, Padera RF, Kuchroo VK, Najafian N, Rothstein DM (2015) Am J Transplant 15(4): 942-53
    › Primary publication · 25645598 (PubMed) · PMC4530122 (PubMed Central)
  10. Tim-1 is essential for induction and maintenance of IL-10 in regulatory B cells and their regulation of tissue inflammation. Xiao S, Brooks CR, Sobel RA, Kuchroo VK (2015) J Immunol 194(4): 1602-8
    › Primary publication · 25582854 (PubMed) · PMC4346345 (PubMed Central)
  11. Mitochondrial dynamics: regulatory mechanisms and emerging role in renal pathophysiology. Zhan M, Brooks C, Liu F, Sun L, Dong Z (2013) Kidney Int 83(4): 568-81
    › Primary publication · 23325082 (PubMed) · PMC3612360 (PubMed Central)
  12. Defect in regulatory B-cell function and development of systemic autoimmunity in T-cell Ig mucin 1 (Tim-1) mucin domain-mutant mice. Xiao S, Brooks CR, Zhu C, Wu C, Sweere JM, Petecka S, Yeste A, Quintana FJ, Ichimura T, Sobel RA, Bonventre JV, Kuchroo VK (2012) Proc Natl Acad Sci U S A 109(30): 12105-10
    › Primary publication · 22773818 (PubMed) · PMC3409739 (PubMed Central)
  13. Kim-1/Tim-1 and immune cells: shifting sands. Ichimura T, Brooks CR, Bonventre JV (2012) Kidney Int 81(9): 809-11
    › Primary publication · 22499138 (PubMed) · PMC3339439 (PubMed Central)
  14. Imaging of podocyte foot processes by fluorescence microscopy. Grgic I, Brooks CR, Hofmeister AF, Bijol V, Bonventre JV, Humphreys BD (2012) J Am Soc Nephrol 23(5): 785-91
    › Primary publication · 22362911 (PubMed) · PMC3338299 (PubMed Central)
  15. Fragmented mitochondria are sensitized to Bax insertion and activation during apoptosis. Brooks C, Cho SG, Wang CY, Yang T, Dong Z (2011) Am J Physiol Cell Physiol 300(3): C447-55
    › Primary publication · 21160028 (PubMed) · PMC3063970 (PubMed Central)
  16. Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Yang L, Besschetnova TY, Brooks CR, Shah JV, Bonventre JV (2010) Nat Med 16(5): 535-43, 1p following 143
    › Primary publication · 20436483 (PubMed) · PMC3928013 (PubMed Central)
  17. Specific mitochondrial calcium overload induces mitochondrial fission in prostate cancer cells. Kaddour-Djebbar I, Choudhary V, Brooks C, Ghazaly T, Lakshmikanthan V, Dong Z, Kumar MV (2010) Int J Oncol 36(6): 1437-44
    › Primary publication · 20428767 (PubMed)
  18. Regulation of mitochondrial dynamics in acute kidney injury in cell culture and rodent models. Brooks C, Wei Q, Cho SG, Dong Z (2009) J Clin Invest 119(5): 1275-85
    › Primary publication · 19349686 (PubMed) · PMC2673870 (PubMed Central)
  19. IFN regulatory factor 8 sensitizes soft tissue sarcoma cells to death receptor-initiated apoptosis via repression of FLICE-like protein expression. Yang D, Wang S, Brooks C, Dong Z, Schoenlein PV, Kumar V, Ouyang X, Xiong H, Lahat G, Hayes-Jordan A, Lazar A, Pollock R, Lev D, Liu K (2009) Cancer Res 69(3): 1080-8
    › Primary publication · 19155307 (PubMed) · PMC2633427 (PubMed Central)
  20. Regulation of mitochondrial morphological dynamics during apoptosis by Bcl-2 family proteins: a key in Bak? Brooks C, Dong Z (2007) Cell Cycle 6(24): 3043-7
    › Primary publication · 18073534 (PubMed)
  21. Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins. Brooks C, Wei Q, Feng L, Dong G, Tao Y, Mei L, Xie ZJ, Dong Z (2007) Proc Natl Acad Sci U S A 104(28): 11649-54
    › Primary publication · 17606912 (PubMed) · PMC1913853 (PubMed Central)
  22. Characterization of cell clones isolated from hypoxia-selected renal proximal tubular cells. Brooks C, Wang J, Yang T, Dong Z (2007) Am J Physiol Renal Physiol 292(1): F243-52
    › Primary publication · 16885151 (PubMed)
  23. Acidic pH inhibits ATP depletion-induced tubular cell apoptosis by blocking caspase-9 activation in apoptosome. Brooks C, Ketsawatsomkron P, Sui Y, Wang J, Wang CY, Yu FS, Dong Z (2005) Am J Physiol Renal Physiol 289(2): F410-9
    › Primary publication · 15755925 (PubMed)